{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T23:19:02Z","timestamp":1774653542033,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"De Nederlandse organisatie voor gezondheidsonderzoek en zorginnovatie","award":["114025003"],"award-info":[{"award-number":["114025003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Intestinal fibrosis is a hallmark of Crohn\u2019s disease. Here, we investigated the impact of several putative antifibrotic compounds on the expression of fibrosis markers using murine precision-cut intestinal slices.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Murine precision-cut intestinal slices were cultured for 48 hours in the presence of profibrotic and\/or antifibrotic compounds. The fibrotic process was studied on gene and protein level using procollagen 1a1 (Col1\u03b11), heat shock protein 47 (Hsp47), fibronectin (Fn2), and plasminogen activator inhibitor-1 (Pai-1). The effects of potential antifibrotic drugs mainly inhibiting the transforming growth factor \u03b2 (TGF-\u03b2) pathway (eg, valproic acid, tetrandrine, pirfenidone, SB203580, and LY2109761) and compounds mainly acting on the platelet-derived growth factor (PDGF) pathway (eg, imatinib, sorafenib, and sunitinib) were assessed in the model at nontoxic concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Murine precision-cut intestinal slices remained viable for 48 hours, and an increased expression of fibrosis markers was observed during culture, including Hsp47, Fn2, and Pai-1. Furthermore, TGF-\u03b21 stimulated fibrogenesis, whereas PDGF did not have an effect. Regarding the tested antifibrotics, pirfenidone, LY2109761, and sunitinib had the most pronounced impact on the expression of fibrosis markers, both in the absence and presence of profibrotic factors, as illustrated by reduced levels of Col1\u03b11, Hsp47, Fn2, and Pai-1 after treatment. Moreover, sunitinib significantly reduced Hsp47 and Fn2 protein expression and the excretion of procollagen 1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Precision-cut intestinal slices can successfully be used as a potential preclinical screening tool for antifibrotic drugs. We demonstrated that sunitinib reduced the expression of several fibrosis markers, warranting further evaluation of this compound for the treatment of intestinal fibrosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izz329","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T14:03:23Z","timestamp":1579183403000},"page":"678-686","source":"Crossref","is-referenced-by-count":11,"title":["Murine Precision-cut Intestinal Slices as a Potential Screening Tool for Antifibrotic Drugs"],"prefix":"10.1093","volume":"26","author":[{"given":"Raditya","family":"Iswandana","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"},{"name":"Faculty of Pharmacy, Universitas Indonesia , Depok, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao Tung","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"},{"name":"Department of Pharmaceutics, Hanoi University of Pharmacy , Hanoi, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Suriguga","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theerut","family":"Luangmonkong","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"},{"name":"Department of Pharmacology, Faculty of Pharmacy, Mahidol University , Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise A","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvette J M","family":"Jansen","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorenda","family":"Oosterhuis","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henricus Antonius","family":"Maria Mutsaers","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"},{"name":"Department of Clinical Medicine, Aarhus University , Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-8452","authenticated-orcid":false,"given":"Peter","family":"Olinga","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen , Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"2023112513161744500_CIT0001","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1572-0241.2006.01010.x","article-title":"Fibrogenesis in Crohn\u2019s disease","volume":"102","author":"Burke","year":"2007","journal-title":"Am J Gastroenterol."},{"key":"2023112513161744500_CIT0002","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000353364","article-title":"Mechanisms of tissue remodeling in inflammatory bowel disease","volume":"31","author":"Rieder","year":"2013","journal-title":"Dig Dis."},{"key":"2023112513161744500_CIT0003","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1136\/gutjnl-2012-304353","article-title":"Crohn\u2019s disease complicated by strictures: a systematic review","volume":"62","author":"Rieder","year":"2013","journal-title":"Gut."},{"key":"2023112513161744500_CIT0004","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.crohns.2014.03.008","article-title":"Results of the 4th scientific workshop of the ECCO (I): pathophysiology of intestinal fibrosis in IBD","volume":"8","author":"Latella","year":"2014","journal-title":"J Crohns Colitis."},{"key":"2023112513161744500_CIT0005","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1620\/tjem.195.21","article-title":"Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease","volume":"195","author":"Kumagai","year":"2001","journal-title":"Tohoku J Exp Med."},{"key":"2023112513161744500_CIT0006","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.crohns.2008.05.009","article-title":"Intestinal fibrosis in inflammatory bowel disease - Current knowledge and future perspectives","volume":"2","author":"Rieder","year":"2008","journal-title":"J Crohns Colitis."},{"key":"2023112513161744500_CIT0007","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1755-1536-4-14","article-title":"Elevated transforming growth factor \u03b2 and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren\u2019s disease fibroblasts","volume":"4","author":"Krause","year":"2011","journal-title":"Fibrogenesis Tissue Repair."},{"key":"2023112513161744500_CIT0008","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.3748\/wjg.v18.i28.3635","article-title":"Cellular and molecular mechanisms of intestinal fibrosis","volume":"18","author":"Speca","year":"2012","journal-title":"World J Gastroenterol."},{"key":"2023112513161744500_CIT0009","first-page":"1283","article-title":"Can we prevent, reduce or reverse intestinal fibrosis in IBD?","volume":"17","author":"Latella","year":"2013","journal-title":"Eur Rev Med Pharmacol Sci."},{"key":"2023112513161744500_CIT0010","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.tiv.2016.01.009","article-title":"Organ- and species-specific biological activity of rosmarinic acid","volume":"32","author":"Iswandana","year":"2016","journal-title":"Toxicol in Vitro."},{"key":"2023112513161744500_CIT0011","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.taap.2018.07.001","article-title":"In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-\u03b2","volume":"355","author":"Luangmonkong","year":"2018","journal-title":"Toxicol Appl Pharmacol."},{"key":"2023112513161744500_CIT0012","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1111\/bph.13945","article-title":"Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis","volume":"174","author":"Luangmonkong","year":"2017","journal-title":"Br J Pharmacol."},{"key":"2023112513161744500_CIT0013","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.taap.2013.11.017","article-title":"Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs","volume":"274","author":"Westra","year":"2014","journal-title":"Toxicol Appl Pharmacol."},{"key":"2023112513161744500_CIT0014","doi-asserted-by":"crossref","first-page":"167sr1","DOI":"10.1126\/scitranslmed.3004700","article-title":"Therapy for fibrotic diseases: nearing the starting line","volume":"5","author":"Friedman","year":"2013","journal-title":"Sci Transl Med."},{"key":"2023112513161744500_CIT0015","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/hep.23334","article-title":"Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo","volume":"51","author":"Mannaerts","year":"2010","journal-title":"Hepatology."},{"key":"2023112513161744500_CIT0016","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1183\/09059180.00001111","article-title":"Antifibrotic activities of pirfenidone in animal models","volume":"20","author":"Schaefer","year":"2011","journal-title":"Eur Respir Rev."},{"key":"2023112513161744500_CIT0017","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.3748\/wjg.v13.i8.1214","article-title":"Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model","volume":"13","author":"Yin","year":"2007","journal-title":"World J Gastroenterol."},{"key":"2023112513161744500_CIT0018","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cytogfr.2004.03.006","article-title":"Regulation of PDGF and its receptors in fibrotic diseases","volume":"15","author":"Bonner","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"2023112513161744500_CIT0019","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1755-1536-7-5","article-title":"Medical therapy of stricturing Crohn\u2019s disease: what the gut can learn from other organs - a systematic review","volume":"7","author":"Bettenworth","year":"2014","journal-title":"Fibrogenesis Tissue Repair."},{"key":"2023112513161744500_CIT0020","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/BF03326410","article-title":"Intestinal subepithelial myofibroblasts in inflammatory bowel diseases","volume":"37 Suppl 14","author":"Andoh","year":"2002","journal-title":"J Gastroenterol."},{"key":"2023112513161744500_CIT0021","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/ki.2011.208","article-title":"Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis","volume":"80","author":"Chen","year":"2011","journal-title":"Kidney Int."},{"key":"2023112513161744500_CIT0022","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2174\/138945010790309984","article-title":"Intestinal fibrosis in Crohn\u2019s disease: medical treatment or surgery?","volume":"11","author":"Spinelli","year":"2010","journal-title":"Curr Drug Targets."},{"key":"2023112513161744500_CIT0023","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3109\/00498254.2012.723151","article-title":"Evaluation of fibrosis in precision-cut tissue slices","volume":"43","author":"Westra","year":"2013","journal-title":"Xenobiotica."},{"key":"2023112513161744500_CIT0024","doi-asserted-by":"crossref","first-page":"G786","DOI":"10.1152\/ajpgi.00059.2012","article-title":"Animal models of intestinal fibrosis: new tools for the understanding of pathogenesis and therapy of human disease","volume":"303","author":"Rieder","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2023112513161744500_CIT0025","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ejphar.2016.06.057","article-title":"Renal fibrosis in precision-cut kidney slices","volume":"790","author":"Stribos","year":"2016","journal-title":"Eur J Pharmacol."},{"issue":"4","key":"2023112513161744500_CIT0026","doi-asserted-by":"crossref","first-page":"e12323","DOI":"10.14814\/phy2.12323","article-title":"Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis","volume":"3","author":"Pham","year":"2015","journal-title":"Physiol Rep"},{"key":"2023112513161744500_CIT0027","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/nprot.2010.111","article-title":"Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies","volume":"5","author":"de Graaf","year":"2010","journal-title":"Nat Protoc."},{"key":"2023112513161744500_CIT0028","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/bjs.5431","article-title":"Expression and regulation of connective tissue growth factor by transforming growth factor beta and tumour necrosis factor alpha in fibroblasts isolated from strictures in patients with Crohn\u2019s disease","volume":"93","author":"Beddy","year":"2006","journal-title":"Br J Surg."},{"key":"2023112513161744500_CIT0029","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/01.sla.0000189606.58343.cd","article-title":"Transforming growth factor-beta promotes pro-fibrotic behavior by serosal fibroblasts via PKC and ERK1\/2 mitogen activated protein kinase cell signaling","volume":"242","author":"Mulsow","year":"2005","journal-title":"Ann Surg."},{"key":"2023112513161744500_CIT0030","doi-asserted-by":"crossref","first-page":"e95462","DOI":"10.1371\/journal.pone.0095462","article-title":"The effect of antifibrotic drugs in rat precision-cut fibrotic liver slices","volume":"9","author":"Westra","year":"2014","journal-title":"Plos One."},{"key":"2023112513161744500_CIT0031","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s10157-016-1365-6","article-title":"Valproic acid attenuates renal fibrosis through the induction of autophagy","volume":"21","author":"Kawaoka","year":"2017","journal-title":"Clin Exp Nephrol."},{"key":"2023112513161744500_CIT0032","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1158\/1541-7786.MCR-07-0324","article-title":"Histone deacetylase inhibitors: overview and perspectives","volume":"5","author":"Dokmanovic","year":"2007","journal-title":"Mol Cancer Res."},{"key":"2023112513161744500_CIT0033","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1471-2466-12-24","article-title":"Pirfenidone inhibits TGF-\u03b21-induced over-expression of collagen type I and heat shock protein 47 in A549 cells","volume":"12","author":"Hisatomi","year":"2012","journal-title":"BMC Pulm Med."},{"key":"2023112513161744500_CIT0034","first-page":"211","article-title":"Effects of pirfenidone on procollagen gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis","volume":"289","author":"Iyer","year":"1999","journal-title":"J Pharmacol Exp Ther."},{"key":"2023112513161744500_CIT0035","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1158\/1078-0432.CCR-11-2855","article-title":"LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-\u03b2 and BMP-associated proinflammatory and proangiogenic signals","volume":"18","author":"Flechsig","year":"2012","journal-title":"Clin Cancer Res."},{"key":"2023112513161744500_CIT0036","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1158\/1535-7163.MCT-07-0337","article-title":"LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis","volume":"7","author":"Melisi","year":"2008","journal-title":"Mol Cancer Ther."},{"issue":"10","key":"2023112513161744500_CIT0037","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"Hata","year":"2012","journal-title":"Nat Rev Drug Discov"},{"key":"2023112513161744500_CIT0038","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-\u03b2 in progression of liver disease","volume":"347","author":"Dooley","year":"2012","journal-title":"Cell Tissue Res."},{"key":"2023112513161744500_CIT0039","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/S0016-5085(03)00403-7","article-title":"Intestinal myofibroblasts in innate immune responses of the intestine","volume":"124","author":"Otte","year":"2003","journal-title":"Gastroenterology."},{"key":"2023112513161744500_CIT0040","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1056\/NEJMra044389","article-title":"Tyrosine kinases as targets for cancer therapy","volume":"353","author":"Krause","year":"2005","journal-title":"N Engl J Med."},{"key":"2023112513161744500_CIT0041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10456-009-9160-6","article-title":"Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?","volume":"13","author":"Gotink","year":"2010","journal-title":"Angiogenesis."},{"key":"2023112513161744500_CIT0042","doi-asserted-by":"crossref","first-page":"7921","DOI":"10.1021\/jm8010299","article-title":"Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states","volume":"51","author":"Kufareva","year":"2008","journal-title":"J Med Chem."},{"key":"2023112513161744500_CIT0043","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nrd2380","article-title":"Molecular basis for sunitinib efficacy and future clinical development","volume":"6","author":"Faivre","year":"2007","journal-title":"Nat Rev Drug Discov."},{"key":"2023112513161744500_CIT0044","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1620\/tjem.239.251","article-title":"Sunitinib, a small-molecule kinase inhibitor, attenuates bleomycin-induced pulmonary fibrosis in mice","volume":"239","author":"Huang","year":"2016","journal-title":"Tohoku J Exp Med."},{"key":"2023112513161744500_CIT0045","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.tiv.2016.05.012","article-title":"Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis","volume":"35","author":"Westra","year":"2016","journal-title":"Toxicol in Vitro."},{"key":"2023112513161744500_CIT0046","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2015.00300","article-title":"New insight into the anti-liver fibrosis effect of multitargeted tyrosine kinase inhibitors: from molecular target to clinical trials","volume":"6","author":"Qu","year":"2016","journal-title":"Front Pharmacol"},{"key":"2023112513161744500_CIT0047","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/hep.22758","article-title":"Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats","volume":"49","author":"Mejias","year":"2009","journal-title":"Hepatology."},{"key":"2023112513161744500_CIT0048","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/MEG.0b013e328365ac54","article-title":"Severe exacerbation of Crohn\u2019s disease during sunitinib treatment","volume":"26","author":"Boers-Sonderen","year":"2014","journal-title":"Eur J Gastroenterol Hepatol."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/5\/678\/5704396","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/5\/678\/5704396","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T13:17:19Z","timestamp":1700918239000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/5\/678\/5704396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,14]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,1,14]]},"published-print":{"date-parts":[[2020,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izz329","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,1,14]]}}}