{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:28:11Z","timestamp":1790270891758,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["114021010"],"award-info":[{"award-number":["114021010"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Liver fibrosis is a major cause of liver\u2010related mortality and, so far, no effective antifibrotic drug is available. Galunisertib, a TGF\u2010\u03b2 receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a human\n                      <jats:italic>ex vivo<\/jats:italic>\n                      model of liver fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Antifibrotic potency and associated mechanisms were studied\n                      <jats:italic>ex vivo<\/jats:italic>\n                      , using both healthy and cirrhotic human precision\u2010cut liver slices. Fibrosis\u2010related parameters, both transcriptional and translational level, were assessed after treatment with galunisertib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Galunisertib showed a prominent antifibrotic potency. Phosphorylation of SMAD2 was inhibited, while that of SMAD1 remained unchanged. In healthy and cirrhotic human livers, spontaneous transcription of numerous genes encoding collagens, including collagen type I, \u03b1 1, collagen maturation, non\u2010collageneous extracellular matrix (ECM) components, ECM remodelling and selected ECM receptors was significantly decreased. The reduction of fibrosis\u2010related transcription was paralleled by a significant inhibition of procollagen I C\u2010peptide released by both healthy and cirrhotic human liver slices. Moreover, galunisertib showed similar antifibrotic potency in human and rat lives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Galunisertib is a drug that deserves to be further investigated for the treatment of liver fibrosis. Inhibition of SMAD2 phosphorylation is probably a central mechanism of action. In addition, blocking the production and maturation of collagens and promoting their degradation are related to the antifibrotic action of galunisertib.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13945","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T07:16:43Z","timestamp":1499671003000},"page":"3107-3117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Evaluating the antifibrotic potency of galunisertib in a human\n                    <i>ex vivo<\/i>\n                    model of liver fibrosis"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-3787","authenticated-orcid":false,"given":"Theerut","family":"Luangmonkong","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"},{"name":"Department of Pharmacology, Faculty of Pharmacy Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Suriguga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Bigaeva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Boersema","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorenda","family":"Oosterhuis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koert P","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Pancreato\u2010Biliary Surgery and Liver Transplantation University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Schuppan","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology and Research Center for Immunotherapy University of Mainz Medical Center  Mainz Germany"},{"name":"Division of Gastroenterology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henricus A M","family":"Mutsaers","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-8452","authenticated-orcid":false,"given":"Peter","family":"Olinga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3810"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13353"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.010"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700271"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2014.934910"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.111"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1257453"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/he.2000.6126"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y"},{"key":"e_1_2_11_13_1","unstructured":"Eli\u2010Lilly(2010).A study of ly2157299 in participants with hepatocellular carcinoma.[Online] Available fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT01246986. 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