Abstract
Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the α3β1integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.
Keywords: basal cell membrane, Nephrin, p38 MAPK signalling, Angiotensin II, VEGF receptor 1
Current Pharmaceutical Design
Title: The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?
Volume: 13 Issue: 26
Author(s): Sally M. Marshall
Affiliation:
Keywords: basal cell membrane, Nephrin, p38 MAPK signalling, Angiotensin II, VEGF receptor 1
Abstract: Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the α3β1integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.
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Cite this article as:
Marshall M. Sally, The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?, Current Pharmaceutical Design 2007; 13 (26) . https://dx.doi.org/10.2174/138161207781662957
DOI https://dx.doi.org/10.2174/138161207781662957 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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