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Wnt-Induced Secreted Protein 1/CCN4 in Liver Fibrosis Both in vitro and in vivo by Yi-cheng Jian, Jin-jun Wang, Shuang Dong, Jun-wei Hu, Li-juan Hu, Gen-mei Yang, Ya-xin Zheng, Wu-jun Xiong

Background: Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown.
Methods: For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-α and TGF-β1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry.
Results: In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-α and in LX-2 cells by TGF-β1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model.
Conclusions: Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.

DOI: 10.7754/Clin.Lab.2013.121035