Email updates

Keep up to date with the latest news and content from BMC Gastroenterology and BioMed Central.

Open Access Research article

Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice

Sebastian Huss15, Christian Stellmacher2, Diane Goltz3, Inna Khlistunova2, Alexander C Adam1, Jonel Trebicka4, Jutta Kirfel3, Reinhard Büttner1 and Ralf Weiskirchen2*

Author Affiliations

1 Institute of Pathology, University of Cologne, Cologne, Germany

2 Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Aachen, Germany

3 Institute of Pathology, University of Bonn, Bonn, Germany

4 Department of Internal Medicine I, University of Bonn, Bonn, Germany

5 Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany

For all author emails, please log on.

BMC Gastroenterology 2013, 13:8  doi:10.1186/1471-230X-13-8

Published: 14 January 2013

Abstract

Background

Four and one half LIM domain protein 2 (FHL2) has been reported to be a key regulator in many cellular processes being associated with fibrogenesis such as cell migration and contraction. Moreover, hepatic FHL2 is involved in regulation pathways mediating proliferation and cell death machineries. We here investigated the role of FHL2 in the setting of experimental and clinical liver fibrosis.

Methods

FHL2−/− and wild type (wt) mice were challenged with CCl4. Fibrotic response was assessed by quantitative real time PCR (qRT-PCR) of fibrotic marker genes, measurement of hydroxyproline content and histological methods. Murine FHL2−/− and hepatic stellate cells (HSC) were isolated and investigated via immunofluorescence. Human fibrotic and normal liver samples were analysed immunohistochemically using antibodies directed against FHL2.

Results

FHL2−/− mice displayed aggravated liver fibrosis compared to wt mice. However, immunofluorescence revealed no significant morphological changes in cultured FHL2−/− and wt myofibroblasts (MFB). In human liver samples, FHL2 was strongly expressed both in the nucleus and cytoplasm in MFB of fibrotic livers. In contrast, FHL2 expression was absent in normal liver tissue.

Conclusions

Deficiency of FHL2 results in aggravation of murine liver fibrosis. In human liver samples, FHL2 is expressed in activated HSCs and portal fibroblasts in human fibrotic livers, pointing to a central role of FHL2 for human hepatic fibrogenesis as well.