{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T21:09:05Z","timestamp":1776805745561,"version":"3.51.2"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan Provincial Health Commission Project","award":["202102071747"],"award-info":[{"award-number":["202102071747"]}]},{"name":"Hunan Provincial Health Commission Project","award":["202202084830"],"award-info":[{"award-number":["202202084830"]}]},{"name":"Hunan Province College Students Research Learning and Innovative Experiment Project","award":["S202510542429"],"award-info":[{"award-number":["S202510542429"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Interleukin-37 (IL-37) is an anti-inflammatory cytokine with an undefined role in chronic endometritis (CE). This study aims to explore its therapeutic mechanism in CE, focusing on epithelial-mesenchymal transition (EMT) and macrophage polarization. A CE model was induced in Sprague-Dawley rats using lipopolysaccharide (LPS), followed by intervention with TAT-fused recombinant IL-37. Histological damage and fibrosis were evaluated through H&amp;E and Masson staining. Immunofluorescence staining was performed to assess the expression of IL-37 and EMT markers (E-cadherin and vimentin) and macrophage phenotypes (M1: CD86+; M2: CD206+). In vitro, transwell, qPCR, Western blot, and flow cytometry analyses were performed to determine the effects of IL-37 on EMT and macrophage polarization. The activity of the STAT6 and Smad3 pathways was evaluated using Western blotting, dual-luciferase assays, and immunofluorescence staining. The results revealed that IL-37 accumulated in the injured uterus, alleviating inflammation, tissue damage, and collagen deposition. IL-37 reduced epithelial migration and reversed abnormal EMT by upregulating E-cadherin expression and downregulating vimentin expression. It also suppressed M1 macrophage infiltration and promoted M2 polarization. Mechanistically, IL-37 coactivated the STAT6 and Smad3 pathways, thereby increasing their phosphorylation and nuclear translocation and elevating ARG1 expression. In conclusion, IL-37 mitigates CE by suppressing EMT and promoting M2 macrophage polarization via coordinated STAT6\/Smad3 activation, highlighting its therapeutic potential for CE.<\/jats:p>","DOI":"10.3390\/cimb48020227","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T13:08:23Z","timestamp":1771592903000},"page":"227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IL-37 Ameliorates Chronic Endometritis by Attenuating Epithelial\u2014Mesenchymal Transition and Promoting M2 Macrophage Polarization"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9447-0401","authenticated-orcid":false,"given":"Zihan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxi","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-5651","authenticated-orcid":false,"given":"Huihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6229-4548","authenticated-orcid":false,"given":"Xia","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","first-page":"538","article-title":"Endometritis\u2014Diagnosis, treatment and its impact on fertility\u2014A scoping review","volume":"26","author":"Singh","year":"2022","journal-title":"JBRA Assist Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ticconi, C., Inversetti, A., Marraffa, S., Campagnolo, L., Arthur, J., Zambella, E., and Di Simone, N. 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