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

BMC Gastroenterol. 2013 Jan 14;13:8. doi: 10.1186/1471-230X-13-8.

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 CCl(4). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carbon Tetrachloride / adverse effects
  • Cell Movement
  • Cells, Cultured
  • Disease Models, Animal
  • Disease Progression*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • LIM-Homeodomain Proteins / deficiency*
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Proteins / deficiency*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Fhl2 protein, mouse
  • LIM-Homeodomain Proteins
  • Muscle Proteins
  • Transcription Factors
  • Carbon Tetrachloride