The Experts below are selected from a list of 1848 Experts worldwide ranked by ideXlab platform
Yasuhiko Ito - One of the best experts on this subject based on the ideXlab platform.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Background Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed Mesangial Proliferative Glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.
Richard J. Johnson - One of the best experts on this subject based on the ideXlab platform.
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experimental Mesangial Proliferative Glomerulonephritis the anti thy 1 1 model
Journal of Nephrology, 1999Co-Authors: J A Jefferson, Richard J. JohnsonAbstract:Abstract The anti-Thy-1.1 model is a rat model of Mesangial Proliferative Glomerulonephritis characterized by initial mesangiolysis followed by Mesangial cell proliferation and accumulation of Mesangial matrix with subsequent resolution and the return to almost normal histology. In this review we discuss the pathogenesis of the initial injury, the mechanisms governing Mesangial cell proliferation and matrix expansion, and some of the processes involved in the resolution of glomerular injury. Understanding these processes of Mesangial cell injury and recovery may provide insights into the pathogenesis of human Mesangial cell diseases such as IgA nephropathy.
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extraglomerular origin of the Mesangial cell after injury a new role of the juxtaglomerular apparatus
Journal of Clinical Investigation, 1997Co-Authors: Christian Hugo, William G Couser, Daniel F Bowenpope, Stuart J. Shankland, Richard J. JohnsonAbstract:: We investigated the origin of the glomerular Mesangial cell, a smooth muscle-like cell that provides structural support in the glomerulus. Injection of anti-Thy 1 antibody that binds the Thy 1 antigen on rat Mesangial cells eliminated (> 95%) the Mesangial population at 20-28 h, while Thy 1-positive cells in the juxtaglomerular apparatus (JGA) were sequestered from the circulation and survived. Single pulse labeling with [3H]thymidine at 36 h labeled Thy 1-positive cells in the JGA and hilus. Serial biopsies demonstrated the progressive migration (5-15 micron/d) and proliferation of these Mesangial reserve cells until the entire glomerulus was repopulated. The regenerating Mesangial population expressed contractile and migratory proteins preferentially at the leading edge of the migratory front. Single as well as multiple pulse labeling with [3H]thymidine confirmed that the entire Mesangial cell repopulation originated from only a few Mesangial reserve cells. These reserve cells resided in the extraglomerular mesangium in the JGA and were not renin-secreting cells, macrophages, smooth muscle cells, or endothelial cells. These studies document Mesangial cell migration in the anti-Thy 1 model of Mesangial Proliferative Glomerulonephritis and provide evidence for a new role for the juxtaglomerular apparatus in the maintenance of the Mesangial cell population.
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changes in cell cycle protein expression during experimental Mesangial Proliferative Glomerulonephritis
Kidney International, 1996Co-Authors: Stuart J. Shankland, William G Couser, Christian Hugo, Steve Coats, Masaomi Nangaku, Raimund H Pichler, Katherine L Gordon, Jeffrey W Pippin, James M Roberts, Richard J. JohnsonAbstract:Changes in cell cycle protein expression during experimental Mesangial Proliferative Glomerulonephritis. A characteristic response to Mesangial cell injury is proliferation, which is closely linked to Mesangial matrix accumulation and the progression of glomerular disease. Cell proliferation in non-renal cells in vitro is regulated at the level of the cell-cycle by specific cyclins and their catalytic partners, cyclin dependent kinases (CDK). Cyclin kinase inhibitors (CKI) prevent proliferation by inhibiting cell-cycle progression. However, the expression of cell-cycle regulatory proteins in the kidney and in renal disease is unknown. To determine this we studied the expression of cell-cycle proteins in vivo in normal rats and rats with experimental Mesangial Proliferative Glomerulonephritis (Thy1 model). Normal quiescent rat glomeruli have a differential expression for CKI's, where p27 Kip1 is highly expressed, and the levels for p21 (Cip1, Waf1, Sdi1, Cap20) (p21) are low. The onset of Mesangial cell proliferation in Thy1 Glomerulonephritis is associated with a reduction in p27 Kip1 levels when Mesangial cell proliferation is maximal. Mesangial cell proliferation in vivo is also associated with an increase in glomerular expression of cyclin A, and an increase in expression and activity for CDK2. The resolution of Mesangial cell proliferation was associated with a return to baseline levels for p27 Kip1 , while the expression for p21 increased substantially. Furthermore, Mesangial cell p21 expression was maintained following the resolution of proliferation. These results provide evidence for a complex interplay of cell-cycle regulatory proteins during the glomerular response to injury in vivo . The marked increase in CDK2 expression during Mesangial cell proliferation and the sustained increase in p21 expression following the resolution of Mesangial cell proliferation suggests that the in vivo expression of certain cell-cycle proteins may differ from that described in non-renal cells in vitro .
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suppression of Mesangial Proliferative Glomerulonephritis development in rats by inhibitors of camp phosphodiesterase isozymes types iii and iv
Journal of Clinical Investigation, 1996Co-Authors: Yasushi Tsuboi, Stuart J. Shankland, Richard J. Johnson, Joseph P Grande, Henry J Walker, Thomas P DousaAbstract:Excessive Mesangial cell (MC) proliferation is a hallmark of many glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P. Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401-410) we found that inhibition of isozyme cyclic-3',5'-nucleotide phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by activating cAMP-dependent protein kinase (PKA) and by decreasing activity of mitogen-activated protein kinase (MAPK). We also found that inhibition of another PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini, C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney Int. 46:28-36). We thus explored whether administration in vivo of the selective PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV antagonist, rolipram (RP), can attenuate development of mesangioProliferative Glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS). Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did not develop proteinuria and maintained normal renal function when examined 5 d after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN-rats the morphology of glomeruli showed a reduction in cellularity compared with control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta -65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a significant reduction of alpha-smooth muscle actin expression by activated MC; in contrast, immunostaining for platelet antigens and laminin were not different. The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats. We conclude that antagonists of PDE-III and PDE-IV administered in submicromolar concentrations in vivo to ATS-injected rats can decrease the activation and proliferation of MC, inhibit the macrophage accumulation, and prevent proteinuria in the acute phase of MSGN. We propose that PDE isozyme inhibitors act to block (negative "crosstalk") the mitogen-stimulated intracellular signaling pathway which controls MC proliferation due to activating of the cAMP-PKA pathway. These results suggest that antagonists of PDE-111 and IV may have a suppressive effect in acute phases or relapses of glomerulopathies associated with MC proliferations.
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rat glomerular Mesangial cells synthesize basic fibroblast growth factor release upregulated synthesis and mitogenicity in Mesangial Proliferative Glomerulonephritis
Journal of Clinical Investigation, 1992Co-Authors: Jurgen Floege, Eudora Eng, Volkard Lindner, Charles E Alpers, Bessie A Young, Michael A Reidy, Richard J. JohnsonAbstract:Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent Mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat Mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in Mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of Glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with Mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent Mesangial Proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as Mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that Mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured Mesangial cells in vivo. Release of Mesangial cell bFGF thus may be an important mechanism involved in the initiation of Mesangial cell proliferation in vivo.
Akihito Yashima - One of the best experts on this subject based on the ideXlab platform.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Background Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed Mesangial Proliferative Glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.
Yukio Yuzawa - One of the best experts on this subject based on the ideXlab platform.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Background Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed Mesangial Proliferative Glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.
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the role of complement in the pathogenesis of tubulointerstitial lesions in rat Mesangial Proliferative Glomerulonephritis
Journal of The American Society of Nephrology, 1997Co-Authors: Yoshiki Morita, Yukio Yuzawa, Atsushi Nomura, Kazuhiro Nishikawa, Nigishi Hotta, Fujio Shimizu, Sejichi MatsuoAbstract:Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary Glomerulonephritis. Mesangial Proliferative Glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with Mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed Glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary Mesangial Proliferative Glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.
Koki Shimada - One of the best experts on this subject based on the ideXlab platform.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Background Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
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Mesangial Proliferative Glomerulonephritis in murine malaria parasite plasmodium chabaudi as infected nc mice
Clinical and Experimental Nephrology, 2017Co-Authors: Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko ItoAbstract:Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed Mesangial Proliferative Glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.