All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-beta1 and Ang II in rat mesangial cells.
OBJECTIVE
To investigate the effect of all-trans RA (atRA) on the increases in plasminogen activator inhibitor-1 (PAI-1) and fibronectin that are induced by transforming growth factor-beta1 (TGF-beta1) and angiotensin II (Ang II) in cultured rat glomerular mesangial cells.


METHODS
Subconfluent glomerular mesangial cells were serum-starved for 48 h and pretreated with atRA with subsequent stimulation of TGF-beta1 and Ang II. Protein expressions of cell-associated fibronectin and PAI-1 in glomerular mesangial cells were evaluated by Western blot analysis. mRNA expression of RA receptors in glomerular mesangial cells was examined by RT-PCR.


RESULTS
Retinoic acid receptor-alpha, -gamma (RAR-alpha, -gamma) and retinoid X receptor-alpha, -beta, -gamma (RXR-alpha, -beta, -gamma) mRNA were expressed in rat glomerular mesangial cells. atRA pretreatment effectively reduced fibronectin expression in glomerular mesangial cells stimulated with TGF-beta 1 or Ang II for 48 h. TGF-beta 1 stimulated PAI-1 expression reached a maximum at 5 h. atRA didn't affect the early (5 h) PAI-1 induction by TGF-beta 1, but markedly attenuated the sustained (48 h) PAI-1 induction. atRA also decreased the prolonged effect of Ang II on PAI-1 expression.


CONCLUSIONS
These results indicate that atRA inhibits the increases in fibronectin that are induced by TGF-beta1 and Ang II in cultured glomerular mesangial cells. The data also suggest that this effect of atRA is associated with a change in PAI-1 levels.
Liu
Xia
X
Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China.
Lü
Lei
L
Tao
Bei-bei
BB
Zhu
Yi-chun
YC
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005353:Fibronectins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D014212:Tretinoin