{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:04:00Z","timestamp":1791497040679,"version":"4.3.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ulcerative colitis (UC) is a chronic gastrointestinal disease characterized by symptoms of abdominal pain and diarrhea. Chymase is a serine protease released by the mast cells and  is highly expressed in patients with UC. However, its role in disease pathogenesis remains poorly understood. In mice, mast cell protease-4 (MCP-4) is considered as the functional homolog of human chymase, sharing similar enzymatic activity and biological roles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the role of MCP-4 in UC, we induced colitis in Mcpt-4-deficient (Mcpt-4<jats:sup>\u2206Cre<\/jats:sup>) and littermate control (Mcpt-4<jats:sup>fl\/fl<\/jats:sup>) mice using 2% dextran sulfate sodium salt (DSS) for 8 days followed by 2 days of water. After sacrifice, colon length was measured, and tissue samples were analyzed by histology (H&amp;amp;E and toluidine blue staining), qPCR, and protein assays. Colonic contents were collected for microbiota and metabolomics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results show that the Mcpt-4-deficiency exacerbated colitis, as reflected by the significantly greater weight loss, higher histological scores, elevated levels of myeloperoxidase and most of determined cytokines. Furthermore, the Mcpt-4<jats:sup>\u2206Cre<\/jats:sup> colitis mice displayed a distinct shift in colonic microbiota composition, notably with significantly increased abundance of bacteria (<jats:italic>Akkermansia<\/jats:italic> and <jats:italic>Turicibacter<\/jats:italic>), associated with potentially worsened inflammation in colitis models. In addition, metabolomic profiling revealed alterations in colonic metabolites involved in key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including NF-kappa B signaling, Th1 and Th2 cell differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings reveal that the mouse chymase MCPT-4 plays important roles in maintaining the intestinal homeostasis during colitis, potentially through regulation of colonic cytokines, microbial and metabolic networks.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1481927","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T05:28:21Z","timestamp":1751952501000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhiqiang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashuang","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"\u00c5brink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3892\/or.16.1.103","article-title":"Immunohistochemical study of chymase-positive mast cells in inflammatory bowel disease","volume":"16","author":"Andoh","year":"2006","journal-title":"Oncol. 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