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Tatsuo Sakai - One of the best experts on this subject based on the ideXlab platform.
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angiotensin ii maintains the structure and function of glomerular Mesangium via type 1a receptor
Virchows Archiv, 1998Co-Authors: Sachiko Inokuchi, Isao Shirato, Kenjiro Kimura, Takeshi Sugaya, Hikaru Yoneda, Kazuo Murakami, Tatsuo SakaiAbstract:The angiotensin II type 1a (AT1a) receptor is the major receptor effecting the multiple actions of angiotensin II on the cardiovascular system. It is expressed abundantly in the glomerular mesangial cells of the kidney. We investigated glomerular changes in null mutant mice minus the AT1a receptor gene to gain an understanding of the in vivo action of angiotensin II via AT1a on the Mesangium. Morphological observations and morphometric analysis revealed that the glomerular volume was greatly increased owing to the expansion of the mesangial area, which contained fluid-filled spaces with a small amount of fibrillar components. The mesangial cells lost contact with each other and with the perimesangial area of the glomerular basement membrane (GBM), so that the glomerular capillary neck was greatly widened. These findings suggest a defect of the anchoring function of mesangial cells resulting from some abnormality in mesangial matrix formation. We conclude that angiotensin II has an important role in the structural and functional maintenance of the Mesangium via the AT1a receptor, especially by reinforcing the connection between mesangial cells and GBM via the mesangial matrix.
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the vascular pole of the renal glomerulus of rat
Advances in Anatomy Embryology and Cell Biology, 1998Co-Authors: Marlies Elger, Tatsuo Sakai, Wilhelm KrizAbstract:: 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
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Three-dimensional analysis of the whole Mesangium in the rat.
Kidney international, 1996Co-Authors: Kazue Inkyo-hayasaka, Tatsuo Sakai, Naoto Kobayashi, Isao Shirato, Yasuhiko TominoAbstract:Three-dimensional analysis of the whole Mesangium in the rat. The three-dimensional structure of the Mesangium was analyzed by means of reconstruction from serial semithin and ultrathin sections of the rat glomerulus. The mesangial domains traced on light micrographs of semithin sections were transferred to styrene models, which were stacked up to reconstruct the whole Mesangium. The reconstructed Mesangium was tree-like in shape and was divided into three lobes that were connected to the vascular pole by a slender neck. The glomerulus contained no islets of Mesangium which were not connected to the vascular pole. The Mesangium contained 64 mesangial loops that were penetrated by capillaries. Reliability of the findings on the mesangial loops was ascertained by various methods including reconstruction of part of the Mesangium from ultrathin sections. Electron microscopic observations revealed that the arms of the mesangial loops were frequently very slender and consisted of mesangial cell processes containing prominent bundles of actin filaments. The mesangial loops were distributed evenly within the Mesangium. Considering previous reports showing about 400 capillary branches in the rat glomerulus as well as the present findings, we concluded that the mesangial loops may change the distribution of intraglomerular blood flow by dynamic contraction of the mesangial cells, or serve as an additional safety device to prevent the expansion of glomerular capillaries.
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widening of capillary neck and alteration of extracellular matrix ultrastructure in diabetic rat glomerulus as revealed by computer morphometry and improved tissue processing
Virchows Archiv, 1993Co-Authors: Isao Shirato, Tatsuo Sakai, Yasuhiko Tomino, Mitsumine Fukui, Hikaru KoideAbstract:Morphological and morphometric studies of glomeruli were carried out in streptozotocin-induced diabetic rats using improved tissue processing and computerized morphometry. Increased mesangial matrix, occupying the enlarged diabetic Mesangium, contained an abundance of dark granular material in addition to the microfibrils which were usually found in the control glomeruli. In the diabetic glomeruli, the lamina densa was thick and heterogeneous showing a dense layer both on its epithelial and endothelial aspects, and the lamina rara externa contained more fibrils than in control rats. Detailed estimation of the absolute values of the various compartments of the diabetic glomeruli by using perfusion-flxed materials and a computer-assisted digitizer revealed that the volume and surface area of the Mesangium were increased more extensively than those of the capillary; the enlargement of the mesangial-capillary interface area was the most pronounced among the morphometric changes of the diabetic glomeruli; and that the moderate increase in capillary volume was associated with an increased radius. Our quantitative results showed that capillaries in the diabetic glomeruli had an extensively wider neck which may be the first sign of structural damage to the glomerular tuft.
Susan V Mclennan - One of the best experts on this subject based on the ideXlab platform.
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mesangial cell derived factors alter monocyte activation and function through inflammatory pathways possible pathogenic role in diabetic nephropathy
American Journal of Physiology-renal Physiology, 2009Co-Authors: Susan V Mclennan, Guy J Lyons, James Bonner, Stephen M TwiggAbstract:Infiltration of macrophages to the kidney is a feature of early diabetic nephropathy. For this to happen monocytes must become activated, migrate from the circulation, and infiltrate the Mesangium....
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effects of Mesangium glycation on matrix metalloproteinase activities possible role in diabetic nephropathy
Diabetes, 2002Co-Authors: Susan V Mclennan, S K Y Martell, Dennis K YueAbstract:High glucose concentrations can decrease degradation of Mesangium by reducing the activities of matrix metalloproteinases (MMPs). The aim of this study was to investigate the effects of glycation of Mesangium matrix on MMP-2, the principal MMP secreted by mesangial cells to degrade type IV collagen. Also examined were membrane type 1 MMP (MT1-MMP), tissue inhibitors of MMPs (TIMP)-1 and -2, and transforming growth factor-β (TGF-β), which together regulate MMP-2 activities in an interacting manner. Human fetal mesangial cells were grown on Mesangium matrix glycated by incubation in 500 mmol/l ribose, with or without aminoguanidine. The activities and gene expression of the abovementioned enzymes/inhibitors were measured by degradation of radiolabeled Mesangium matrix, RT-PCR, and zymography. Glycation of Mesangium matrix resulted in a threefold increase in advance glycation end products and reduced by 45% the matrix-degrading activity of MMPs secreted by mesangial cells. Analogous to the direct effects of high glucose concentrations, glycation of matrix increased the gene expression of MMP-2 and TIMP-1 (control 100 ± 16.9 vs. glycated 197.3 ± 30.6% and control 100 ± 5.3 vs. glycated 152.1 ± 20.1%, respectively; P < 0.05) and decreased MT1-MMP (control 100 ± 1.17 vs. glycated 54.1 ± 15.2%; P < 0.05). However, unlike high glucose concentrations, glycation was not associated with decreased activation of MMP-2. Similarly, glycation but not high glucose increased expression of TIMP-2 (control 100 ± 5.9 vs. glycated 168.2 ± 31.4%; P < 0.05), and the effects of glycation on degradation can be abolished by anti-TIMP-2 antibody. Glycation of matrix decreased TGF-β mRNA by 38.2% and total and active TGF-β by 35.5 and 21.5%, respectively, opposite the effects of high glucose concentrations. Our results indicate that glycation of matrix affects the balance between MMP-2 and its activator and inhibitors, but this phenomenon is not due to TGF-β. The process of glycation may impart to the Mesangium matrix a memory effect that contributes to the long-term toxicity of hyperglycemia.
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high glucose concentration causes a decrease in Mesangium degradation a factor in the pathogenesis of diabetic nephropathy
Diabetes, 1994Co-Authors: Susan V Mclennan, Elizabeth J Fisher, Dennis K Yue, J R TurtleAbstract:Mesangium enlargement is a constant feature of diabetic nephropathy and is likely to be important in the pathogenesis of this diabetic complication. Whether decreased degradation of Mesangium plays any role in causing the enlargement is uncertain. We developed a system of preparing radioactively labeled Mesangium matrix from mesangial cell cultures to be used as substrates for studies of Mesangium degradation. Degradation is commenced by growing mesangial cells on the labeled matrix and monitored by the release of radioactivity into the culture medium. High glucose concentration (30 mM), whether present 1) when the matrix is being made or 2) when the degradation is taking place, reduces the rate of Mesangium degradation. The second but not the first of these two phenomena was abolished by aminoguanidine. Phorbol 12-myristate 13-acetate, added in a manner to antagonize the action of protein kinase C, inhibited Mesangium degradation and was not able to nullify the effect of high glucose. Thus it appears unlikely that a high glucose concentration inhibits Mesangium degradation by increasing mesangial cell protein kinase C activity. We conclude that decreased degradation of Mesangium as a result of hyperglycemia may play a role in causing the Mesangium enlargement that occurs in diabetic nephropathy.
Jeffrey I Kreisberg - One of the best experts on this subject based on the ideXlab platform.
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the glomerular Mesangium in diabetes mellitus
Kidney International, 1993Co-Authors: Jeffrey I Kreisberg, Suzanne H AyoAbstract:The glomerular Mesangium in diabetes mellitus. Like the renal glomerular Mesangium in patients with diabetic nephropathy, glomerular mesangial cell cultures grown in 30 mM glucose accumulate increased amounts of the extracellular matrix (ECM) proteins fibronectin, laminin, and type IV collagen. This is due to increased ECM protein synthesis and mRNA levels. Similar to other cells types that are affected by the diabetic state (such as, vascular cells and peripheral nerve), mesangial cells transport glucose by an insulin-independent, facilitated diffusion transport system. Kinetic studies reveal that intracellular glucose levels may reach the ambient glucose concentrations achieved in diabetes. Growth studies reveal that glucose does not exert its effect on mesangial cell ECM accumulation by affecting cell growth, but rather it causes an increase in diacylglycerol (DAG) mass and activates protein kinase C. Agents such as phorbol myristate acetate (PMA) and the cell permeable DAG analogue, oleoyl acetyl glycerol (OAG) which activate protein kinase C also increase ECM mRNAs. These results implicate protein kinase C activation in the increased ECM accumulation observed in mesangial cell cultures grown in high glucose.
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increased extracellular matrix synthesis and mrna in mesangial cells grown in high glucose medium
American Journal of Physiology-renal Physiology, 1991Co-Authors: Robert A Radnik, William F Glass, Jo Ann Garoni, Elaine R Rampt, Dean R Appling, Jeffrey I KreisbergAbstract:Nodular expansion of glomerular Mesangium with increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular Mesangium, accumulate 50–60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulse-chase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S [( 35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were exam...
Isao Shirato - One of the best experts on this subject based on the ideXlab platform.
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angiotensin ii maintains the structure and function of glomerular Mesangium via type 1a receptor
Virchows Archiv, 1998Co-Authors: Sachiko Inokuchi, Isao Shirato, Kenjiro Kimura, Takeshi Sugaya, Hikaru Yoneda, Kazuo Murakami, Tatsuo SakaiAbstract:The angiotensin II type 1a (AT1a) receptor is the major receptor effecting the multiple actions of angiotensin II on the cardiovascular system. It is expressed abundantly in the glomerular mesangial cells of the kidney. We investigated glomerular changes in null mutant mice minus the AT1a receptor gene to gain an understanding of the in vivo action of angiotensin II via AT1a on the Mesangium. Morphological observations and morphometric analysis revealed that the glomerular volume was greatly increased owing to the expansion of the mesangial area, which contained fluid-filled spaces with a small amount of fibrillar components. The mesangial cells lost contact with each other and with the perimesangial area of the glomerular basement membrane (GBM), so that the glomerular capillary neck was greatly widened. These findings suggest a defect of the anchoring function of mesangial cells resulting from some abnormality in mesangial matrix formation. We conclude that angiotensin II has an important role in the structural and functional maintenance of the Mesangium via the AT1a receptor, especially by reinforcing the connection between mesangial cells and GBM via the mesangial matrix.
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Three-dimensional analysis of the whole Mesangium in the rat.
Kidney international, 1996Co-Authors: Kazue Inkyo-hayasaka, Tatsuo Sakai, Naoto Kobayashi, Isao Shirato, Yasuhiko TominoAbstract:Three-dimensional analysis of the whole Mesangium in the rat. The three-dimensional structure of the Mesangium was analyzed by means of reconstruction from serial semithin and ultrathin sections of the rat glomerulus. The mesangial domains traced on light micrographs of semithin sections were transferred to styrene models, which were stacked up to reconstruct the whole Mesangium. The reconstructed Mesangium was tree-like in shape and was divided into three lobes that were connected to the vascular pole by a slender neck. The glomerulus contained no islets of Mesangium which were not connected to the vascular pole. The Mesangium contained 64 mesangial loops that were penetrated by capillaries. Reliability of the findings on the mesangial loops was ascertained by various methods including reconstruction of part of the Mesangium from ultrathin sections. Electron microscopic observations revealed that the arms of the mesangial loops were frequently very slender and consisted of mesangial cell processes containing prominent bundles of actin filaments. The mesangial loops were distributed evenly within the Mesangium. Considering previous reports showing about 400 capillary branches in the rat glomerulus as well as the present findings, we concluded that the mesangial loops may change the distribution of intraglomerular blood flow by dynamic contraction of the mesangial cells, or serve as an additional safety device to prevent the expansion of glomerular capillaries.
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widening of capillary neck and alteration of extracellular matrix ultrastructure in diabetic rat glomerulus as revealed by computer morphometry and improved tissue processing
Virchows Archiv, 1993Co-Authors: Isao Shirato, Tatsuo Sakai, Yasuhiko Tomino, Mitsumine Fukui, Hikaru KoideAbstract:Morphological and morphometric studies of glomeruli were carried out in streptozotocin-induced diabetic rats using improved tissue processing and computerized morphometry. Increased mesangial matrix, occupying the enlarged diabetic Mesangium, contained an abundance of dark granular material in addition to the microfibrils which were usually found in the control glomeruli. In the diabetic glomeruli, the lamina densa was thick and heterogeneous showing a dense layer both on its epithelial and endothelial aspects, and the lamina rara externa contained more fibrils than in control rats. Detailed estimation of the absolute values of the various compartments of the diabetic glomeruli by using perfusion-flxed materials and a computer-assisted digitizer revealed that the volume and surface area of the Mesangium were increased more extensively than those of the capillary; the enlargement of the mesangial-capillary interface area was the most pronounced among the morphometric changes of the diabetic glomeruli; and that the moderate increase in capillary volume was associated with an increased radius. Our quantitative results showed that capillaries in the diabetic glomeruli had an extensively wider neck which may be the first sign of structural damage to the glomerular tuft.
Bernd R Sterzel - One of the best experts on this subject based on the ideXlab platform.
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adhesion molecules in the glomerular Mesangium
Kidney International, 1997Co-Authors: Stefan Gauer, Jian Yao, Harald Schoecklmann, Bernd R SterzelAbstract:Experimental evidence indicates that extensive "cross-talk" exists between glomerular cells, extracellular matrix molecules and soluble mediator substances affecting the proliferative and secretory phenotype of glomerular mesangial cells. Both matrix and cytokines regulate mesangial cell behavior in vitro and in vivo after binding to specific cell surface receptors. It appears as if the concerted action of insoluble and soluble ligands on mesangial cells involves a reciprocal regulation of matrix molecules and cytokines as well as expression and affinity of their respective receptors. Elucidation of the potential biologic and clinical relevance of cell-matrix interactions in the glomerular Mesangium represents a challenging goal in current kidney research. This brief review summarizes recent investigations concerning regulation of expression and function of adhesion molecules and matrix receptors in the Mesangium. In addition to results from cell culture studies, descriptive findings on expression and regulation of adhesion molecules and their potential role for altered mesangial cell behavior in glomerular disease is considered.
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cell matrix interactions in the glomerular Mesangium
Kidney International, 1996Co-Authors: Harald D Rupprecht, Harald O Schocklmann, Bernd R SterzelAbstract:Cell-matrix interactions in the glomerular Mesangium. Specific interactions between cells and components of the surrounding extracellular matrix (ECM) or underlying basement membrane have been shown to modulate cell behavior, including cellular responses to soluble regulator molecules. In addition to the long-recognized role of such interactions in cell localization, anchoring and differentiation during embryogenesis, they are also involved in diverse processes such as maintenance of tissue integrity, response of cells to mechanical stress, inflammatory response, wound healing, tumor cell growth and metastasis as well as apoptosis. Over the last several years, evidence has been reported that extensive "cross-talk" between glomerular mesangial cells (MCs), ECM molecules and soluble mediator substances also affects the proliferative and synthetic phenotype of MCs. This is likely to be relevant for the behavior of MCs during embryonic development, tissue repair and disease processes of glomeruli. The potential biologic and clinical relevance of cell-matrix interactions in the glomerulus makes their elucidation a challenging goal in current kidney research. In this brief review, we present selected aspects of recent investigations concerning the mesangial matrix and its interactions with MCs. In addition to results from cell culture studies, descriptive findings on abnormalities of the ECM and their potential role for the altered MC behavior in glomerular disease will also be discussed.