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

Abstract

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 36 h. 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.

• Authors: Tokunari Okayama, Shojiro Kikuchi, Toshiya Ochiai, Hisashi Ikoma, Takeshi Kubota, Daisuke Ichikawa, Hitoshi Fujiwara, Kazuma Okamoto, Chouhei Sakakura, Teruhisa Sonoyama, Yukihito Kokuba, Yoshinori Doi, Sachiko Tsukita, D Montgomery Bissell, Eigo Otsuji
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1782 Issue 9 Pg. 542-8 (Sep 2008) ISSN: 0006-3002 [Print] Netherlands
• PMID: 18606220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytoskeletal Proteins
• Membrane Proteins
• Microfilament Proteins
• ezrin
• moesin
• radixin
• Collagen

Topics

• Animals
• Bile Ducts (pathology)
• Cautery
• Cell Movement
• Cells, Cultured
• Collagen (biosynthesis)
• Cytoskeletal Proteins (metabolism)
• Hepatocytes (pathology)
• Hot Temperature
• Ligation
• Liver (metabolism, pathology)
• Liver Cirrhosis, Experimental (metabolism, pathology)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Microfilament Proteins (deficiency, metabolism)
• Wound Healing