RÉSUMÉ
<p><b>OBJECTIVE</b>To observe the effect of ligand of peroxisome proliferators-activated receptor gamma (PPAR gamma) 15d-PGJ2 on the proliferation and activation of hepatic stellate cells (HSC) and to study the role played by PPAR gamma during the process of HSC activation.</p><p><b>METHODS</b>By using RT-PCR and cell culture, we investigated the effects of 5 micro mol/L and 10 micro mol/L 15d-PGJ2 on culture-activated HSC and on PDGF-induced HSC proliferation, production of extracellular matrix and expression of chemokines.</p><p><b>RESULTS</b>The expression of alpha-SMA was significantly suppressed by 5mumol/L 15d-PGJ2, and the expression of PPAR gamma was significantly higher in the 15d-PGJ2 treated group than in the untreated group (0.64+/-0.03 vs 0.09+/-0.01, t=36.0517, P<0.01); PDGF-induced HSC proliferation was dose-dependently suppressed by 15d-PGJ2; the expressions of PPAR gamma in 5 micro mol/L and also in 10 micro mol/L 15d-PGJ2 plus PDGF pre-treated group increased much more than those in the PDGF-treated group (0.03+/-0.02 vs 0.60+/-0.03, t=42.6616, P<0.01 and 0.03+/-0.02 vs 0.69+/-0.04, t=33.83, P<0.01); the expressions of alpha-SMA, alpha 1 (I)-collagen and MCP-1 were suppressed.</p><p><b>CONCLUSION</b>Activation of PPAR gamma can modulate pro-fibrotic and pro-inflammatory roles of HSC and the increased expression of PPAR gamma may become a new target for antifibrosis.</p>
Sujet(s)
Animaux , Mâle , Rats , Différenciation cellulaire , Prolifération cellulaire , Cellules cultivées , Cellules étoilées du foie , Biologie cellulaire , Métabolisme , Récepteur PPAR gamma , Métabolisme , Prostaglandine D2 , Pharmacologie , Rat WistarRÉSUMÉ
<p><b>OBJECTIVES</b>To observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC).</p><p><b>METHODS</b>By morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN).</p><p><b>RESULTS</b>In vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week.</p><p><b>CONCLUSION</b>The expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.</p>