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- Title
Dual effects of angiotensin 11 on the plasminogen/plasmin system in rat mesangial cells.
- Authors
Kagami, Shoji; Kuhara, Takashi; Okada, Kaname; Kuroda, Yasuhiro; Border, Wayne A.; Noble, Nancy A.
- Abstract
Dual effects of angiotensin II on the plasminogen/plasmin system in rat mesangial cells. Previous studies indicate that angiotensin II (Ang II) stimulates extracellular matrix synthesis through induction of transforming growth factor-β (TGF-β) expression. Here we investigate Ang II effects on the plasmin protease system. Plasmin both degrades extracellular matrix itself and activates metalloproteinases which then degrade collagens. Plasmin production is determined by the balance between plasminogen activators (PA) and their inhibitors (PAI-1,2). The data presented here indicate that Ang II treatment of mesangial cells in culture markedly increases PAI-1 gene transcription and PAI-1 mRNA levels but does not change the half life of Pal-l mRNA. Increased PAI-l protein was detected 24 hours after Ang II stimulation with a concomitant decrease of PA activity. To determine whether these effects were mediated by TGF-β cells were coincubated with Ang II and neutralizing antibody to TGF-β. Induction of PAI-1 at four hours was not altered but the prolonged effect of Ang II on PAI-1 protein synthesis was markedly diminished. Thus, Ang II acts both through rapid, direct transcriptional up-regulation of the Pal-1 gene and through induction of TGF-β, providing sustained changes in the PAI-l/PA system, which would favor extracellular matrix accumulation by inhibiting turnover. These data provide further evidence that Ang II can act as a potent fibrogenic molecule independent of its effects on blood pressure.
- Subjects
ANGIOTENSINS; OLIGOPEPTIDES; PLASMIN; CELLS; COLLAGEN; MESSENGER RNA
- Publication
Kidney International, 1997, Vol 51, Issue 3, p664
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1997.96