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Cell and Tissue Research

, Volume 347, Issue 1, pp 129–140

First Online: 04 May 2011Received: 17 February 2011Accepted: 04 April 2011


In patients with progressive podocyte disease, such as focal segmental glomerulosclerosis FSGS and membranous nephropathy, upregulation of transforming growth factor-ß TGF-ß is observed in podocytes. Mechanical pressure or biomechanical strain in podocytopathies may cause overexpression of TGF-ß and angiotensin II Ang II. Oxidative stress induced by Ang II may activate the latent TGF-ß, which then activates Smads and Ras-extracellular signal-regulated kinase ERK signaling pathways in podocytes. Enhanced TGF-ß activity in podocytes may lead to thickening of the glomerular basement membrane GBM by overproduction of GBM proteins and impaired GBM degradation in podocyte disease. It may also lead to podocyte apoptosis and detachment from the GBM, and epithelial-mesenchymal transition EMT of podocytes, initiating the development of glomerulosclerosis. Furthermore, activated TGF-ß-Smad signaling by podocytes may induce connective tissue growth factor and vascular endothelial growth factor overexpression, which could act as a paracrine effector mechanism on mesangial cells to stimulate mesangial matrix synthesis. In proliferative podocytopathies, such as cellular or collapsing FSGS, TGF-ß-induced ERK activation may play a role in podocyte proliferation, possibly via TGF-ß-induced EMT of podocytes. Collectively, these data bring new mechanistic insights into our understanding of the TGF-ß overexpression by podocytes in progressive podocyte disease.

KeywordsAngiotensin II Biomechanical strain Glomerular basement membrane thickening Glomerulosclerosis Mesangial matrix expansion Podocyte growth  Download fulltext PDF

Autor: Hyun Soon Lee


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