{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:34Z","timestamp":1760146654222,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\/3626-2022"],"award-info":[{"award-number":["RGPIN\/3626-2022"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The impaired mucosal barrier is a hallmark of ulcerative colitis (UC), an inflammatory colonic disorder with epidemiological and pathophysiology sex bias. UC Patients overexpress the colonic epithelial cells (CECs)-derived peptide pancreastatin (PST). Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, has shown promising anti-inflammatory effects on UC. However, no data exist in the context of CEC barrier function and integrity. We investigated the impact of PSTi8 treatment on CECs in homeostatic and colitic conditions. PSTi8 (2.5 mg\/mL\/kg, i.r.) or PBS treatment started one day before colitis induction (5% dextran sodium sulfate for five days) in male and female C57BL\/6 mice. The disease activity score was assessed daily. Epithelial-associated cytokines, markers specific to differentiation, proliferation, differentiated CECs, stem cells, CECs regulators, and the PSTi8 G-protein coupled receptor 78 (GPR78) signaling pathway, were evaluated using ELISA, immunofluorescence and qRT-PCR. PSTi8 treatment reduced the epithelial-associated cytokines and differentiated CECs while promoting CEC proliferation and self-renewal in females at a steady state through the GRP78 signaling pathway. PSTi8 treatment exacerbated colitis severity and increased CEC differentiation while reducing proliferation in colitic females. Conversely, PSTi8 treatment reduced males\u2019 susceptibility to colitis by preserving stem cells and differentiated CECs. PST regulated colonic mucosal maintenance in a sex- and disease-dependent manner.<\/jats:p>","DOI":"10.3390\/ijms252312757","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T10:05:56Z","timestamp":1732701956000},"page":"12757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner"],"prefix":"10.3390","volume":"25","author":[{"given":"Diane M.","family":"Tshikudi","sequence":"first","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5092-7882","authenticated-orcid":false,"given":"Hannah","family":"Hutchison","sequence":"additional","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Eric","family":"Ghia","sequence":"additional","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada"},{"name":"Children\u2019s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB R3A 1R9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rees, W.D., Tandun, R., Yau, E., Zachos, N.C., and Steiner, T.S. 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