Publication: Differential role of mesangial cells
and podocytes in TGF-ß-induced mesangial
matrix synthesis in chronic glomerular disease
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Date
2009
Authors
Lee, Hyun Soon ; Song, Chi Young
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Glomerulosclerosis is characterized by
mesangial matrix accumulation that is mediated
primarily by activation of transforming growth factor-ß
(TGF-ß). Unlike podocytes, mesangial cells secrete
TGF-ß in response to common in vitro fibrogenic
stimuli. However, mesangial immunostaining for active
TGF-ß1 in chronic glomerular disease is almost
negligible, despite increased mesangial TGF-ß1 mRNA
expression, while podocytes covering the sclerotic
glomerular segments exhibit increased TGF-ß1 protein
expression. The mechanisms whereby TGF-ß is
activated in the diseased glomeruli and how the activated
TGF-ß leads to mesangial matrix overproduction are not
clear. We provide evidence that TGF-ß secreted as latent
complexes by mesangial cells is stored in the mesangial
matrix, from which soluble forms of latent TGF-ß are
released and localized to the podocyte surface in chronic
glomerular disease. Podocyte-derived reactive oxygen
species, plasmin and thrombospondin-1, particularly
renin-angiotensin-aldosterone system-induced oxidative
stress, seem to be involved in TGF-ß activation in
podocytes. We also provide evidence that the TGF-ß-
induced secretion of connective tissue growth factor and
vascular endothelial growth factor by podocytes acts as a
paracrine regulatory mechanism on mesangial cells,
which may cause mesangial matrix accumulation
culminating in the development of glomerulosclerosis.
Collectively, these data bring new insights into our
understanding of the roles of the mesangial cells and
podocytes in the TGF-ß-induced mesangial matrix
synthesis in chronic glomerular disease.
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