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Role of ERK1/2 and p38 mitogen-activated protein kinases in the regulation of thrombospondin-1 by TGF-β1 in rat proximal tubular cells and mouse fibroblasts

Title
Role of ERK1/2 and p38 mitogen-activated protein kinases in the regulation of thrombospondin-1 by TGF-β1 in rat proximal tubular cells and mouse fibroblasts
Authors
Nakagawa T.Lan H.Y.Glushakova O.Zhu H.J.Kang D.-H.Schreiner G.F.Bottinger E.P.Johnson R.J.Sautin Y.Y.
Ewha Authors
강덕희
SCOPUS Author ID
강덕희scopus
Issue Date
2005
Journal Title
Journal of the American Society of Nephrology
ISSN
1046-6673JCR Link
Citation
Journal of the American Society of Nephrology vol. 16, no. 4, pp. 899 - 904
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Thrombospondin-1 (TSP-1) inhibits angiogenesis and activates latent TGF-β1, both of which are strongly associated with progression of renal disease. Recently, it was reported that Smad2 but not Smad3 regulates TSP-1 expression in response to TGF-β1 in rat tubular epithelial cells as well as in mouse fibroblasts. This study investigated the role of ERK1/2 and p38 mitogen-activated protein kinases (MAPK). TGF-β1 activated both ERK1/2 and p38 in the rat proximal tubular cell line NRK52E. Blocking ERK1/2 and p38 inhibited TGF-β1-induced TSP-1 mRNA and protein expression. Next, the cross-talk between Smad2 and ERK1/2 or p38 was examined. Whereas blocking of ERK1/2 or p38 failed to inhibit TGF-β1-induced Smad2 activation, inhibition of Smad2 by Smad7 overexpression inhibited the phosphorylation of ERK1/2 but not p38 in response to TGF-β1. Similar results were observed using mouse fibroblasts from Smad2 knockout embryos, in that TGF-β1 was able to activate p38 but not ERK1/2 in this cell line. In conclusion, TSP-1 expression is regulated by both ERK1/2 and p38 MAPK in rat proximal tubular cells and mouse fibroblasts in response to TGF-β1. The ERK1/2 activation is dependent on Smad2 activation, whereas the p38 activation occurs independent of Smad2. Because TSP-1 is a major antiangiogenic molecule and an activator of TGF-β1, this provides an important insight to the mechanism by which TGF-β1 may mediate interstitial fibrosis and progressive renal disease. Copyright © 2005 by the American Society of Nephrology.
DOI
10.1681/ASN.2004080689
Appears in Collections:
의과대학 > 의학과 > Journal papers
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