Protease-activated receptor-2 modulates hepatic stellate cell collagen release and apoptotic status.
The pathogenesis of hepatic fibrosis is to be further investigated. Protease-activated receptor-2 (PAR2) plays a role in hepatic fibrosis. This study aims to elucidate the role of activation of PAR2 in the regulation of hepatic stellate cell activities. In this study, the expression of PAR2, Fas and caveolin-1 in human hepatic stellate cell line, HHStec cell (HHStecs) was assessed by real time RT-PCR and Western blot. The levels of collagen were determined by enzyme-linked immunosorbent assay. The PAR2 gene was silenced in HHStecs using RNA interference. Apoptosis of HHStecs was assessed by flow cytometry. The results showed that HHStecs expressed PAR2, which was up regulated by activation with phorbol myristate acetate (PMA). Activation of PAR2 increased the release of collagen from HHStecs. Exposure to PMA induced HHStec apoptosis, which was significantly inhibited by activation of PAR2. The PAR2 activation also suppressed the expression of caveolin-1 and Fas in HHStecs. Over expression of caveolin-1 in HHStecs blocked PAR2-reduced apoptosis. We conclude that HHStecs express PAR2. Activation of PAR2 increases HHStecs to release collagen and reduces the activation-induced HHStec apoptosis, which can be inhibited by the over expression of caveolin-1.
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Jiang-Lin
JL
Li
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Wen-song
WS
Cai
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Fei
F
Shen
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Zhe
Z
Feng
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Guang-Hui
GH
Zhu
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Jie
J
Cao
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: BoXu44@163.com.
Bo
B
Xu
D017209:Apoptosis; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D051242:Caveolin 1; D044464:Receptor, PAR-2; D003094:Collagen
Apoptosis; Collagen; Hepatic fibrosis; Hepatic stellate cells; Protease-activated receptor 2