{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:56:01Z","timestamp":1781279761571,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Groningen Research Institute for Pharmacy (GRIP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In Crohn\u2019s Disease (CD), intestinal fibrosis is a prevalent yet unresolved complication arising from chronic and transmural inflammation. The histological assessment of CD intestines shows changes in tissue morphology in all the layers, including the mucosa and muscularis. This study aimed to determine the differences in fibrogenesis between mucosa and muscularis. Human precision-cut intestinal slices (hPCIS) were prepared from human intestine mucosa and muscularis and treated with TGF-\u03b21 and\/or PDGF-BB for 72 h. Gene and protein expression and matrix metalloproteinase (MMP) activity were determined. The basal gene expression of various fibrosis markers was higher in muscularis compared to mucosa hPCIS. During incubation, Pro-Collagen-1A1 secretion increased in muscularis but not in mucosa hPCIS. MMP gene expression increased during incubation in mucosa and muscularis hPCIS, except for MMP9, MMP12, and MMP13 in muscularis hPCIS. Incubation with TGF-\u03b21 caused increased COL1A1 expression in the mucosa but not in muscularis hPCIS. In muscularis hPCIS, TGF-\u03b21 treatment caused a decrease in MMP1 and CTSK expression, while MMP13 was increased. In the presence of TGF-\u03b21, protease inhibitor expression was stable, except for SERPINE1, which was increased in muscularis hPCIS. We conclude that fibrogenesis is more pronounced in muscularis hPCIS compared to mucosa hPCIS, especially when stimulated with TGF-\u03b21.<\/jats:p>","DOI":"10.3390\/cells13131084","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T03:53:43Z","timestamp":1719201223000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fibrogenesis in Human Mucosa and Muscularis Precision-Cut Intestinal Slices"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-1857","authenticated-orcid":false,"given":"Carin","family":"Biel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniek","family":"Kastermans","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Heidema","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4787-5563","authenticated-orcid":false,"given":"Martin","family":"Pehrsson","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Henstra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Mortensen","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas Nico","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Centre Groningen, 9713 GZ 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, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12990","DOI":"10.1111\/sji.12990","article-title":"Mechanism of Fibrosis and Stricture Formation in Crohn\u2019s Disease","volume":"92","author":"Alfredsson","year":"2020","journal-title":"Scand. 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