{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:38:57Z","timestamp":1770820737783,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K15431"],"award-info":[{"award-number":["16K15431"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16J09463"],"award-info":[{"award-number":["16J09463"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Interestingly, Pin1 knockout (KO) mice exhibited significant attenuation of DSS-induced colitis compared to wild-type (WT) mice, based on various parameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase-3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1-type macrophages in the colon was decreased in the Pin1 KO mice while that of M2-type macrophages was increased. Moreover, Pin1 KO mice showed downregulation of both Il17 and Il23a expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS-induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD.<\/jats:p>","DOI":"10.3390\/cells10051230","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T12:19:57Z","timestamp":1621253997000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pathological Role of Pin1 in the Development of DSS-Induced Colitis"],"prefix":"10.3390","volume":"10","author":[{"given":"Yasuka","family":"Matsunaga","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan"},{"name":"Research Fellow of Japan Society for the Promotion of Science, Tokyo 102-0083, 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disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrgastro.2015.34","article-title":"Epidemiology and risk factors for IBD","volume":"12","author":"Ananthakrishnan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-019-1844-5","article-title":"Somatic inflammatory gene mutations in human ulcerative colitis epithelium","volume":"577","author":"Nanki","year":"2019","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.cell.2015.10.072","article-title":"Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis","volume":"163","author":"Nowarski","year":"2015","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nakatsu, Y., Matsunaga, Y., Yamamotoya, T., Ueda, K., Inoue, Y., Mori, K., Sakoda, H., Fujishiro, M., Ono, H., and Kushiyama, A. (2016). 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Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S1097-2765(03)00490-8","article-title":"Regulation of NF-kappa B signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65\/RelA","volume":"12","author":"Ryo","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/ncb2629","article-title":"ERK1\/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect","volume":"14","author":"Yang","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/21650","article-title":"The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein","volume":"399","author":"Lu","year":"1999","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/ni1266","article-title":"The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils","volume":"6","author":"Shen","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24255","DOI":"10.1074\/jbc.M115.658559","article-title":"Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the \u03b3 subunit","volume":"290","author":"Nakatsu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44526","DOI":"10.1074\/jbc.M112.397133","article-title":"Role of Pin1 protein in the pathogenesis of nonalcoholic steatohepatitis in a rodent model","volume":"287","author":"Nakatsu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/ni.2031","article-title":"The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF","volume":"12","author":"Ciric","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1084\/jem.20081463","article-title":"Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis","volume":"206","author":"Conti","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1182\/blood-2009-04-216085","article-title":"Evidence for a cross-talk between human neutrophils and Th17 cells","volume":"115","author":"Pelletier","year":"2010","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ibd.20753","article-title":"Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis","volume":"15","author":"Alex","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.autrev.2013.06.004","article-title":"Innate and adaptive immunity in inflammatory bowel disease","volume":"13","author":"Geremia","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shen, Z.J., Hu, J., Shiizaki, K., Kuro-o, M., and Malter, J.S. (2016). Phosphate-Induced Renal Fibrosis Requires the Prolyl Isomerase Pin1. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150093"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5795","DOI":"10.1182\/blood-2010-03-273094","article-title":"The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils","volume":"116","author":"Boussetta","year":"2010","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.4049\/jimmunol.1800881","article-title":"TLR-7 Stress Signaling in Differentiating and Mature Eosinophils Is Mediated by the Prolyl Isomerase Pin1","volume":"201","author":"Shen","year":"2018","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1053\/j.gastro.2011.02.012","article-title":"Interactions between the host innate immune system and microbes in inflammatory bowel disease","volume":"140","author":"Abraham","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3748\/wjg.v20.i1.6","article-title":"Immunopathology of inflammatory bowel disease","volume":"20","author":"Wallace","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature06878","article-title":"TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function","volume":"453","author":"Zhou","year":"2008","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature14452","article-title":"Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation","volume":"523","author":"Gagliani","year":"2015","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/ni.2027","article-title":"ROR\u03b3t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation","volume":"12","author":"Codarri","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6999","DOI":"10.4049\/jimmunol.177.10.6999","article-title":"The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes","volume":"177","author":"Esnault","year":"2006","journal-title":"J. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:02:52Z","timestamp":1760162572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cells10051230"],"URL":"https:\/\/doi.org\/10.3390\/cells10051230","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]}}}