{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:07:09Z","timestamp":1770970029103,"version":"3.50.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,1,14]],"date-time":"2013-01-14T00:00:00Z","timestamp":1358121600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>FHL2<jats:sup>\u2212\/\u2212<\/jats:sup> and wild type (wt) mice were challenged with CCl<jats:sub>4<\/jats:sub>. Fibrotic response was assessed by quantitative real time PCR (qRT-PCR) of fibrotic marker genes, measurement of hydroxyproline content and histological methods. Murine FHL2<jats:sup>\u2212\/\u2212<\/jats:sup> and hepatic stellate cells (HSC) were isolated and investigated <jats:italic>via<\/jats:italic> immunofluorescence. Human fibrotic and normal liver samples were analysed immunohistochemically using antibodies directed against FHL2.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>FHL2<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed aggravated liver fibrosis compared to wt mice. However, immunofluorescence revealed no significant morphological changes in cultured FHL2<jats:sup>\u2212\/\u2212<\/jats:sup> 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-230x-13-8","type":"journal-article","created":{"date-parts":[[2013,1,14]],"date-time":"2013-01-14T09:13:57Z","timestamp":1358154837000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice"],"prefix":"10.1186","volume":"13","author":[{"given":"Sebastian","family":"Huss","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Stellmacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Goltz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna","family":"Khlistunova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander C","family":"Adam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonel","family":"Trebicka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"Kirfel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,1,14]]},"reference":[{"issue":"1","key":"863_CR1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1582-4934.2006.tb00292.x","volume":"10","author":"AM Gressner","year":"2006","unstructured":"Gressner AM, Weiskirchen R: Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med. 2006, 10 (1): 76-99. 10.1111\/j.1582-4934.2006.tb00292.x.","journal-title":"J Cell Mol Med"},{"issue":"18","key":"863_CR2","doi-asserted-by":"publisher","first-page":"12001","DOI":"10.1074\/jbc.272.18.12001","volume":"272","author":"R Konrat","year":"1997","unstructured":"Konrat R, Weiskirchen R, Krautler B, Bister K: Solution structure of the carboxyl-terminal LIM domain from quail cysteine-rich protein CRP2. J Biol Chem. 1997, 272 (18): 12001-12007. 10.1074\/jbc.272.18.12001.","journal-title":"J Biol Chem"},{"issue":"20","key":"863_CR3","doi-asserted-by":"publisher","first-page":"7127","DOI":"10.1021\/bi973055v","volume":"37","author":"G Kontaxis","year":"1998","unstructured":"Kontaxis G, Konrat R, Krautler B, Weiskirchen R, Bister K: Structure and intramodular dynamics of the amino-terminal LIM domain from quail cysteine- and glycine-rich protein CRP2. Biochemistry. 1998, 37 (20): 7127-7134. 10.1021\/bi973055v.","journal-title":"Biochemistry"},{"issue":"1\u20132","key":"863_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S0925-4773(99)00314-7","volume":"91","author":"I Bach","year":"2000","unstructured":"Bach I: The LIM domain: regulation by association. Mech Dev. 2000, 91 (1\u20132): 5-17.","journal-title":"Mech Dev"},{"issue":"43","key":"863_CR5","doi-asserted-by":"publisher","first-page":"33669","DOI":"10.1074\/jbc.M002519200","volume":"275","author":"V Wixler","year":"2000","unstructured":"Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M: The LIM-only protein DRAL\/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes. J Biol Chem. 2000, 275 (43): 33669-33678. 10.1074\/jbc.M002519200.","journal-title":"J Biol Chem"},{"issue":"1","key":"863_CR6","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1083\/jcb.200606043","volume":"177","author":"V Wixler","year":"2007","unstructured":"Wixler V, Hirner S, Muller JM, Gullotti L, Will C, Kirfel J, Gunther T, Schneider H, Bosserhoff A, Schorle H, et al: Deficiency in the LIM-only protein Fhl2 impairs skin wound healing. J Cell Biol. 2007, 177 (1): 163-172. 10.1083\/jcb.200606043.","journal-title":"J Cell Biol"},{"issue":"20","key":"863_CR7","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1016\/j.yexcr.2008.09.023","volume":"314","author":"J Kirfel","year":"2008","unstructured":"Kirfel J, Pantelis D, Kabba M, Kahl P, Roper A, Kalff JC, Buettner R: Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism. Exp Cell Res. 2008, 314 (20): 3684-3691. 10.1016\/j.yexcr.2008.09.023.","journal-title":"Exp Cell Res"},{"issue":"12","key":"863_CR8","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1038\/labinvest.2011.109","volume":"91","author":"L Gullotti","year":"2011","unstructured":"Gullotti L, Czerwitzki J, Kirfel J, Propping P, Rahner N, Steinke V, Kahl P, Engel C, Schule R, Buettner R, et al: FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer. Lab Invest. 2011, 91 (12): 1695-1705. 10.1038\/labinvest.2011.109.","journal-title":"Lab Invest"},{"issue":"5","key":"863_CR9","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.jhep.2012.06.035","volume":"57","author":"Y Nouet","year":"2012","unstructured":"Nouet Y, Dahan J, Labalette C, Levillayer F, Julien B, Jouvion G, Cairo S, Vives FL, Ribeiro A, Huerre M, et al: The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis. J Hepatol. 2012, 57 (5): 1029-1036. 10.1016\/j.jhep.2012.06.035.","journal-title":"J Hepatol"},{"issue":"1","key":"863_CR10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1755-1536-3-10","volume":"3","author":"S Huss","year":"2010","unstructured":"Huss S, Schmitz J, Goltz D, Fischer HP, Buttner R, Weiskirchen R: Development and evaluation of an open source Delphi-based software for morphometric quantification of liver fibrosis. Fibrogenesis Tissue Repair. 2010, 3 (1): 10-10.1186\/1755-1536-3-10.","journal-title":"Fibrogenesis Tissue Repair"},{"issue":"6","key":"863_CR11","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1111\/j.1478-3231.2011.02496.x","volume":"31","author":"J Trebicka","year":"2011","unstructured":"Trebicka J, Racz I, Siegmund SV, Cara E, Granzow M, Schierwagen R, Klein S, Wojtalla A, Hennenberg M, Huss S, et al: Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts. Liver Int. 2011, 31 (6): 860-870. 10.1111\/j.1478-3231.2011.02496.x.","journal-title":"Liver Int"},{"issue":"1","key":"863_CR12","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/hep.21673","volume":"46","author":"J Trebicka","year":"2007","unstructured":"Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M, Nevens F, Sauerbruch T, Heller J: Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA\/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology. 2007, 46 (1): 242-253. 10.1002\/hep.21673.","journal-title":"Hepatology"},{"issue":"1","key":"863_CR13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1586\/egh.11.92","volume":"6","author":"F Tacke","year":"2012","unstructured":"Tacke F, Weiskirchen R: Update on hepatic stellate cells: pathogenic role in liver fibrosis and novel isolation techniques. Expert Rev Gastroenterol Hepatol. 2012, 6 (1): 67-80. 10.1586\/egh.11.92.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"3","key":"863_CR14","doi-asserted-by":"publisher","first-page":"179","DOI":"10.2310\/6650.2002.33431","volume":"50","author":"EA Kruglov","year":"2002","unstructured":"Kruglov EA, Jain D, Dranoff JA: Isolation of primary rat liver fibroblasts. J Investig Med. 2002, 50 (3): 179-184. 10.2310\/6650.2002.33431.","journal-title":"J Investig Med"},{"issue":"4","key":"863_CR15","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.cellsig.2010.12.002","volume":"23","author":"SK Meurer","year":"2011","unstructured":"Meurer SK, Tihaa L, Borkham-Kamphorst E, Weiskirchen R: Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibrogenic Smad signalling. Cell Signal. 2011, 23 (4): 683-699. 10.1016\/j.cellsig.2010.12.002.","journal-title":"Cell Signal"},{"issue":"8","key":"863_CR16","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1210\/me.2011-1347","volume":"26","author":"CK Matulis","year":"2012","unstructured":"Matulis CK, Mayo KE: The LIM Domain Protein FHL2 Interacts with the NR5A Family of Nuclear Receptors and CREB to Activate the Inhibin-alpha Subunit Gene in Ovarian Granulosa Cells. Mol Endocrinol. 2012, 26 (8): 1278-1290. 10.1210\/me.2011-1347.","journal-title":"Mol Endocrinol"},{"issue":"3","key":"863_CR17","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1093\/emboj\/19.3.359","volume":"19","author":"JM Muller","year":"2000","unstructured":"Muller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schule R: FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J. 2000, 19 (3): 359-369. 10.1093\/emboj\/19.3.359.","journal-title":"EMBO J"},{"issue":"7","key":"863_CR18","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1096\/fj.07-095521","volume":"22","author":"J Park","year":"2008","unstructured":"Park J, Will C, Martin B, Gullotti L, Friedrichs N, Buettner R, Schneider H, Ludwig S, Wixler V: Deficiency in the LIM-only protein FHL2 impairs assembly of extracellular matrix proteins. FASEB J. 2008, 22 (7): 2508-2520. 10.1096\/fj.07-095521.","journal-title":"FASEB J"},{"issue":"19","key":"863_CR19","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.1016\/j.yexcr.2007.05.023","volume":"313","author":"ZL Gao","year":"2007","unstructured":"Gao ZL, Deblis R, Glenn H, Schwartz LM: Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis. Exp Cell Res. 2007, 313 (19): 4000-4014. 10.1016\/j.yexcr.2007.05.023.","journal-title":"Exp Cell Res"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-230X-13-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-230X-13-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-230X-13-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-230X-13-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T21:52:58Z","timestamp":1630533178000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgastroenterol.biomedcentral.com\/articles\/10.1186\/1471-230X-13-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,14]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["863"],"URL":"https:\/\/doi.org\/10.1186\/1471-230x-13-8","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,14]]},"assertion":[{"value":"2 August 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"8"}}