Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 296, Issue 2, Pages F337-F346Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.90437.2008
Keywords
renin-angiotensin system; glomerulus; receptor Mas; extracellular matrix protein; transforming growth factor-beta 1
Categories
Funding
- Canadian Institutes of Health Research [11560]
- Kidney Foundation of Canada
Ask authors/readers for more resources
Zimpelmann J, Burns KD. Angiotensin-(1-7) activates growth-stimulatory pathways in human mesangial cells. Am J Physiol Renal Physiol 296: F337-F346, 2009. First published December 3, 2008; doi:10.1152/ajprenal.90437.2008.-Angiotensin-(1-7) [Ang-(1-7)] is generated in part via ACE2-dependent degradation of angiotensin II (ANG II). In proximal tubular cells, Ang-(1-7) inhibits ANG II-stimulated phosphorylation of the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-related kinase (ERK1/ERK2), and c-jun N-terminal kinase (JNK), suggesting that Ang-(1-7) protects against ANG II-mediated tubulointerstitial injury. We determined the effect of Ang-(1-7) on signaling and growth responses in cultured human mesangial cells. Ang-(1-7) increased phosphorylation of p38, ERK1/ERK2, and JNK MAPKs, which was blocked by the Ang-(1-7) antagonist A-779. Neither the AT(1) receptor antagonist losartan, nor the AT(2) antagonist PD123319 affected specific binding of [I-125] Ang-(1-7) or Ang-(1-7)-stimulated p38 phosphorylation. Ang-(1-7) increased cell arachidonic acid release, an effect blocked by A-779. The p38 MAPK antagonist SB202190 completely prevented Ang-(1-7)-stimulated release of arachidonic acid, whereas inhibitors of ERK or JNK had no effect. Ang-(1-7) significantly enhanced DNA synthesis and increased production of transforming growth factor-beta 1 ( TGF-beta 1), fibronectin, and collagen IV. Both A-779 and SB202190 blocked the Ang-(1-7)-stimulated increases in TGF-beta 1, fibronectin, and collagen IV. These data indicate that Ang-(1-7) activates MAPK phosphorylation via binding to a specific receptor in human mesangial cells. Stimulation of p38 MAPK phosphorylation by Ang-(1-7) leads to release of arachidonic acid and production of TGF-beta 1 and extracellular matrix proteins. We conclude that Ang-(1-7) exerts growth-stimulatory effects in human mesangial cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available