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

Sebastian Huss, Christian Stellmacher, Diane Goltz, Inna Khlistunova, Alexander C. Adam, Jonel Trebicka, Jutta Kirfel, Reinhard Büttner, Ralf Weiskirchen*

*Corresponding author for this work
5 Citations (Scopus)

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.

Original languageEnglish
Article number8
JournalBMC Gastroenterology
Volume13
Issue number1
DOIs
Publication statusPublished - 14.01.2013

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