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- Title
Renin-stimulated TGF-β1 expression is regulated by a mitogen-activated protein kinase in mesangial cells.
- Authors
Huang, Y.; Noble, N. A.; Zhang, J.; Xu, C.; Border, W. A.
- Abstract
Recent evidence indicates that renin itself might be profibrotic, independent of angiotensin II; however, the signaling system by which renin exerts a direct effect is not known. We tested the hypothesis that renin receptor activation, in turn, activates the extracellular-signal regulated kinase 1 and 2 (ERK1/2) of the mitogen-activated protein kinase system in mesangial cells. Recombinant rat renin induced a rapid phosphorylation of ERK1/2 and subsequent cell proliferation in a dose- and time-dependent manner. ERK1/2 activation by renin addition was not altered by angiotensin-converting enzyme inhibition or angiotensin receptor blockade. An ERK kinase inhibitor significantly reduced the renin-induced ERK1/2 phosphorylation and the subsequent increase in transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 mRNA expression. A small-inhibiting RNA, siRNA, against the renin receptor completely blocked ERK1/2 activation by rat renin. We conclude that renin induces ERK1/2 activation though a receptor-mediated, angiotensin II-independent mechanism in mesangial cells. This renin-activated pathway triggers cell proliferation along with TGF-β1 and plasminogen activator inhibitor-1 gene expression. This system may play an important role in the overall profibrotic actions of renin.Kidney International (2007) 72, 45–52; doi:10.1038/sj.ki.5002243; published online 28 March 2007
- Subjects
RENIN; ANGIOTENSIN II; MITOGENS; PROTEIN kinases; CELLS
- Publication
Kidney International, 2007, Vol 72, Issue 1, p45
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/sj.ki.5002243