Wnt signaling enhances the activation and survival of human hepatic stellate cells

Edited by Veli-Pekka Lehto

Received 25 January 2007; received in revised form 9 May 2007; accepted 18 May 2007. published online 30 May 2007.

Abstract

Wnt signaling was implicated in pulmonary and renal fibrosis. Since Wnt activity is enhanced in liver cirrhosis, Wnt signaling may also participate in hepatic fibrogenesis. Thus, we determined if Wnt signaling modulates hepatic stellate cell (HSC) activation and survival. Wnt3A treatment significantly activated human HSCs, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells. Wnt3A treatment significantly suppressed TRAIL-induced apoptosis in control HSCs versus sFRP1 over-expressing cells. Particularly, caspase 3 was more activated in sFRP1 over-expressing cells following TRAIL and Wnt3A treatment. These observations imply that Wnt signaling promotes hepatic fibrosis by enhancing HSC activation and survival.

Keywords: Hepatic stellate cell, Fibrosis, Wnt, Secreted frizzled-related protein 1, Apoptosis

a Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

b Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

Corresponding author. Fax: +82 2 743 6701.

PII: S0014-5793(07)00584-4

doi:10.1016/j.febslet.2007.05.050

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