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Wilhelm Kriz - One of the best experts on this subject based on the ideXlab platform.

  • Oxford Textbook of Clinical Nephrology - The Renal Glomerulus
    Oxford Medicine Online, 2015
    Co-Authors: Marlies Elger, Wilhelm Kriz
    Abstract:

    The Glomerulus performs its functions with three major cell types. Endothelial cells and visceral epithelial cells (podocytes) lie on the inside and outside of the glomerular basement membrane, and together these three structures form the glomerular filtration barrier. Mesangial cells sit in the axial region. Pathologies of all these regions and cell types can be identified. Parietal epithelial cells lining Bowman’s capsule participate in crescent formation, and at the tubular pole some of these cells seem to represent a stem cell population for tubular cells and podocytes. The extraglomerular mesangium and juxtaglomerular apparatus complete the description of the glomerular corpuscle. The structure of these elements, and how they relate to function, are illustrated in detail.

  • The Vascular Pole of the Renal Glomerulus of Rat - The vascular pole of the Renal Glomerulus of rat.
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    1 Introduction.- 2 Material and Methods.- 3 Results.- 3.1 The Opening in Bowman's Capsulex.- 3.1.1 Transition of the GMB into the PBM.- 3.1.2 Transition from Podocytes to Parietal Cells.- 3.2 Glomerular Arterioles.- 3.2.1 Afferent Arteriole.- 3.2.2 Efferent Arteriole.- 3.3 Extraglomerular Mesangium.- 3.3.1 EGM Cells.- 3.3.2 EGM Matrix.- 3.3.3 EGM Relationships to Neighboring Structures.- 3.3.4 Glomerular Stalk.- 4 Discussion.- 4.1 Stabilization of the Vascular Pole.- 4.2 Regulation of Glomerular Blood Flow and Filtration.- 4.3 Integration of Vascular Pole Structures into the Juxtaglomerular Apparatus.- 4.4 Fluid Leakage Through the Glomerular Stalk.- 5 Summary.- References.

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

Tatsuo Sakai - One of the best experts on this subject based on the ideXlab platform.

  • Evolutionary morphology of podocytes and primary urine-producing apparatus
    Anatomical Science International, 2017
    Co-Authors: Koichiro Ichimura, Tatsuo Sakai
    Abstract:

    Excretory organs were acquired in the early phase of metazoan evolution, and they play a crucial role in the maintenance of homeostasis of body fluids. In general, these organs consist of two functional components, the primary-urine producing apparatus and the modulating tubule. This basic organization of the excretory organs is conserved among most metazoans. Herein, we present an overview of the morphological evolution of the primary urine-producing apparatus in metazoans and describe the acquisition of the Renal Glomerulus—a specialized primary urine-producing apparatus—in vertebrates. We also describe the advancement of the glomerular structure and function in higher vertebrates.

  • sirp α cd47 system functions as an intercellular signal in the Renal Glomerulus
    American Journal of Physiology-renal Physiology, 2010
    Co-Authors: Hidetake Kurihara, Yutaka Harita, Koichiro Ichimura, Seisuke Hattori, Tatsuo Sakai
    Abstract:

    The Renal Glomerulus consists of endothelial cells, podocytes, and mesangial cells. These cells cooperate with each other for glomerular filtration; however, the intercellular signaling molecules between glomerular cells are not fully determined. Tyrosine phosphorylation of slit diaphragm molecules is a key to the detection of the signal to podocytes from other cells. Although src kinase is involved in this event, the molecules working for dephosphorylation remain unclear. We demonstrate that signal-inhibitory regulatory protein (SIRP)-α, which recruits a broadly distributed tyrosine dephosphorylase SHP-2 to the plasma membrane, is located in podocytes. SIRP-α is a type I transmembrane glycoprotein, which has three immunoglobulin-like domains in the extracellular region and two SH2 binding motifs in the cytoplasm. This molecule functions as a scaffold for many proteins, especially the SHP-2 molecule. SIRP-α is concentrated in the slit diaphragm region of normal podocytes. CD47, a ligand for SIRP-α, is also expressed in the Glomerulus. CD47 is located along the plasma membrane of mesangial cells, but not on podocytes. CD47 is markedly decreased during mesangiolysis, but increased in mesangial cells in the restoration stage. SIRP-α is heavily tyrosine phosphorylated under normal conditions; however, tyrosine phosphorylation of SIRP-α was markedly decreased during mesangiolysis induced by Thy1.1 monoclonal antibody injection. It is known that the cytoplasmic domain of SIPR-α is dephosphorylated when CD47 binds to the extracellular domain of SIRP-α. The data suggest that the CD47-SIRP-α interaction may be functionally important in cell-cell communication in the diseased Glomerulus.

  • The Vascular Pole of the Renal Glomerulus of Rat - The vascular pole of the Renal Glomerulus of rat.
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    1 Introduction.- 2 Material and Methods.- 3 Results.- 3.1 The Opening in Bowman's Capsulex.- 3.1.1 Transition of the GMB into the PBM.- 3.1.2 Transition from Podocytes to Parietal Cells.- 3.2 Glomerular Arterioles.- 3.2.1 Afferent Arteriole.- 3.2.2 Efferent Arteriole.- 3.3 Extraglomerular Mesangium.- 3.3.1 EGM Cells.- 3.3.2 EGM Matrix.- 3.3.3 EGM Relationships to Neighboring Structures.- 3.3.4 Glomerular Stalk.- 4 Discussion.- 4.1 Stabilization of the Vascular Pole.- 4.2 Regulation of Glomerular Blood Flow and Filtration.- 4.3 Integration of Vascular Pole Structures into the Juxtaglomerular Apparatus.- 4.4 Fluid Leakage Through the Glomerular Stalk.- 5 Summary.- References.

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

Masanori Kitamura - One of the best experts on this subject based on the ideXlab platform.

  • creation of a reversible on off system for site specific in vivo control of exogenous gene activity in the Renal Glomerulus
    Proceedings of the National Academy of Sciences of the United States of America, 1996
    Co-Authors: Masanori Kitamura
    Abstract:

    Abstract Using genetically engineered glomerular mesangial cells, an in vivo gene transfer approach was developed that specifically targets the Renal Glomerulus. By combining this system with a tetracycline (Tc)-responsive promoter, the present study aimed to create a reversible on/off system for site-specific in vivo control of exogenous gene activity within the Glomerulus. In the Tc regulatory system, a Tc-controlled transactivator (tTA) encoded by a regulator plasmid induces target gene transcription by binding to a tTA-responsive promoter located in a response plasmid. Tc inhibits this tTA-dependent transactivation via its affinity for tTA. In double-transfected cells, therefore, the activity of a transgene can be controlled by Tc. Cultured rat mesangial cells were cotransfected with a regulator plasmid and a response plasmid that introduces a beta-galactosidase gene. In vitro, stable double-transfectant MtTAG cells exhibited no beta-galactosidase activity in the presence of Tc. However, following withdrawal of Tc from culture media, expression of beta-galactosidase was induced within 24 h. When Tc was again added, the expression was rapidly resuppressed. Low concentrations of Tc were sufficient to maintain the silent state of tTA-dependent promoter. MtTAG cells were then transferred into the rat glomeruli via Renal artery injection. In the isolated chimeric glomeruli, expression of beta-galactosidase was induced ex vivo in the absence of Tc, whereas it was repressed in its presence. When Tc-pretreated MtTAG cells were transferred into the glomeruli of untreated rats, beta-galactosidase expression was induced in vivo within 3 days. Oral administration of Tc dramatically suppressed this induction. These data demonstrate the feasibility of using mesangial cell vectors combined with the Tc regulatory system for site-specific in vivo control of exogenous gene expression in the Glomerulus.

  • gene transfer into the rat Renal Glomerulus via a mesangial cell vector site specific delivery in situ amplification and sustained expression of an exogenous gene in vivo
    Journal of Clinical Investigation, 1994
    Co-Authors: Masanori Kitamura, Robert J. Unwin, S Taylor, Fujio Shimizu, S Burton, Leon G Fine
    Abstract:

    To evaluate the pathophysiological function of specific molecules in the Renal Glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the Renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the Glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the Glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.

Marlies Elger - One of the best experts on this subject based on the ideXlab platform.

  • Oxford Textbook of Clinical Nephrology - The Renal Glomerulus
    Oxford Medicine Online, 2015
    Co-Authors: Marlies Elger, Wilhelm Kriz
    Abstract:

    The Glomerulus performs its functions with three major cell types. Endothelial cells and visceral epithelial cells (podocytes) lie on the inside and outside of the glomerular basement membrane, and together these three structures form the glomerular filtration barrier. Mesangial cells sit in the axial region. Pathologies of all these regions and cell types can be identified. Parietal epithelial cells lining Bowman’s capsule participate in crescent formation, and at the tubular pole some of these cells seem to represent a stem cell population for tubular cells and podocytes. The extraglomerular mesangium and juxtaglomerular apparatus complete the description of the glomerular corpuscle. The structure of these elements, and how they relate to function, are illustrated in detail.

  • The Vascular Pole of the Renal Glomerulus of Rat - The vascular pole of the Renal Glomerulus of rat.
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    1 Introduction.- 2 Material and Methods.- 3 Results.- 3.1 The Opening in Bowman's Capsulex.- 3.1.1 Transition of the GMB into the PBM.- 3.1.2 Transition from Podocytes to Parietal Cells.- 3.2 Glomerular Arterioles.- 3.2.1 Afferent Arteriole.- 3.2.2 Efferent Arteriole.- 3.3 Extraglomerular Mesangium.- 3.3.1 EGM Cells.- 3.3.2 EGM Matrix.- 3.3.3 EGM Relationships to Neighboring Structures.- 3.3.4 Glomerular Stalk.- 4 Discussion.- 4.1 Stabilization of the Vascular Pole.- 4.2 Regulation of Glomerular Blood Flow and Filtration.- 4.3 Integration of Vascular Pole Structures into the Juxtaglomerular Apparatus.- 4.4 Fluid Leakage Through the Glomerular Stalk.- 5 Summary.- References.

  • the vascular pole of the Renal Glomerulus of rat
    Advances in Anatomy Embryology and Cell Biology, 1998
    Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm Kriz
    Abstract:

    : In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The Glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

Leon G Fine - One of the best experts on this subject based on the ideXlab platform.

  • gene transfer into the rat Renal Glomerulus via a mesangial cell vector site specific delivery in situ amplification and sustained expression of an exogenous gene in vivo
    Journal of Clinical Investigation, 1994
    Co-Authors: Masanori Kitamura, Robert J. Unwin, S Taylor, Fujio Shimizu, S Burton, Leon G Fine
    Abstract:

    To evaluate the pathophysiological function of specific molecules in the Renal Glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the Renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the Glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the Glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.