Attenuated response to liver injury in moesin-deficient mice: Impaired stellate cell migration and decreased fibrosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Article

Kikuchi, Shojiro¹  Doi, Yoshinori²  Tsukita, Sachiko³  Bissell, D. Montgomery^4,5 

[1] Kyoto Prefectural Univ Med, Dept Surg, Div Digest Dis, Kamigyo Ku, Kyoto 6028566, Japan

[2] Otemae Hosp, Dept Internal Med, Chuo Ku, Osaka 5400008, Japan

[3] Osaka Univ, Biol Sci Lab, Organismal Biosyst Lab, Grad Sch Frontier Biosci,Dept Pathol,Grad Sch Med, Suita, Osaka 5650871, Japan

[4] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA

关键词: ERM;    thermal denaturation;    wound healing;    anti-fibrotic;    collagen synthesis;   

DOI  :  10.1016/j.bbadis.2008.06.006

来源: Elsevier

【 摘 要 】

Hepatic stellate cells (HSCs) respond to injury with a coordinated set of events (termed activation), which includes migration and upregulation of matrix protein production. Cell migration requires an intact actin cytoskeleton that is linked to the plasma membrane by ezrin-radixin-moesin (ERM) proteins. We have previously found that the linker protein in HSCs is exclusively moesin. Here, we describe HSC migration and fibrogenesis in moesin-deficient mice. We developed an acute liver injury model that involved focal thermal denaturation and common bile duct ligation. HSC migration and collagen deposition were assessed by immunohistology and quantitative real-time PCR. Activated HSCs were isolated from wild-type or moesin-deficient mice for direct examination of migration. Activated HSCs from wild-type mice were positive for moesin. Migration of moesin-deficient HSCs was significantly reduced. in a culture assay, 22.1% of normal HSCs migrated across a filter in 36h. In contrast, only 1.3% of activated moesin-deficient HSCs migrated. Collagen deposition around the injury area similarly was reduced in moesin-deficient liver. The linker protein moesin is essential for HSC activation and migration in response to injury. Fibrogenesis is coupled to migration and reduced in moesin-deficient mice. Agents that target moesin may be beneficial for chronic progressive fibrosis. (C) 2008 Elsevier B.V. All rights reserved.

【 授权许可】

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