Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions

Naoki Uyama ¹, Liena Zhao ², Elke Van Rossen ¹, Yoshiaki Hirako ³, Hendrik Reynaert ¹, David H Adams ⁴, Zhigang Xue ⁵, Zhenlin Li ⁵, Richard Robson ⁶, Milos Pekny ⁷ and Albert Geerts ^1*

¹ Laboratory for Cell Biology, Vrije Universiteit Brussel (VUB), Belgium
² Centre for Liver Research, University of Newcastle-upon-Tyne, United Kingdom
³ Division of Biological Science, Nagoya University, Japan
⁴ Medical Research Council Centre for Immune Regulation, University of Birmingham, United Kingdom
⁵ CNRS UMR7079, Université Pierre et Marie Curie, Paris, France
⁶ Muscle Biology Group, Departments of Biochemistry and Animal Science, Iowa State University, United States
⁷ The Arvid Carlsson Institute, Institute of Clinical Neuroscience, Göteborg University, Sweden

^* To whom correspondence should be addressed. E-mail: bert{at}cyto.vub.ac.be.

Accepted 7 February 2006

Abstract

Background: In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. Aim: We investigated the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs).

Methods: In isolated and cultured rat HSCs, synemin expression was examined by (Q)RT-PCR, Western blotting and immunocytochemistry. Protein-protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy.

Results: Expression of synemin was significantly down-regulated with increased culture time. We showed in 1day- cultured HSCs that synemin associates with other IF proteins (GFAP, desmin and vimentin), and with focal adhesion proteins, vinculin and talin, but not with - actinin or paxillin. Synemin IF and focal adhesion proteins co-localized in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immmunohistochemistry. In normal rat and human livers, we found synemin immunoreactivity in HSCs, smooth muscle cells of hepatic arterioles, and in nerve bundles in portal tracts, but not in portal fibroblasts. In CCl₄-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. In conclusion, synemin is expressed in quiescent HSCs, but not in portal fibroblasts. Synemin expression decreases with HSC activation in vivo during chronic liver damage and with HSC activation in culture.

Conclusion: Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.

Keywords: desmin, glial fibrillary acidic protein, liver, vimentin, vinculin

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