title: Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice.
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.
authors: Institute of Pathology, University of Cologne, Cologne, Germany.
authors: Sebastian
authors: S
authors: Huss
authors: Christian
authors: C
authors: Stellmacher
authors: Diane
authors: D
authors: Goltz
authors: Inna
authors: I
authors: Khlistunova
authors: Alexander C
authors: AC
authors: Adam
authors: Jonel
authors: J
authors: Trebicka
authors: Jutta
authors: J
authors: Kirfel
authors: Reinhard
authors: R
authors: Büttner
authors: Ralf
authors: R
authors: Weiskirchen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C491382:Fhl2 protein, mouse; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D002251:Carbon Tetrachloride