TY - JOUR
T1 - Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice
AU - Huss, Sebastian
AU - Stellmacher, Christian
AU - Goltz, Diane
AU - Khlistunova, Inna
AU - Adam, Alexander C.
AU - Trebicka, Jonel
AU - Kirfel, Jutta
AU - Büttner, Reinhard
AU - Weiskirchen, Ralf
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/1/14
Y1 - 2013/1/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872155481&partnerID=8YFLogxK
U2 - 10.1186/1471-230X-13-8
DO - 10.1186/1471-230X-13-8
M3 - Journal articles
C2 - 23311569
AN - SCOPUS:84872155481
SN - 1471-230X
VL - 13
JO - BMC Gastroenterology
JF - BMC Gastroenterology
IS - 1
M1 - 8
ER -