{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:01:55Z","timestamp":1782280915936,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,26]]},"group-title":"Genomics","reference-count":145,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                  genital tract infection is linked to severe reproductive complications in women, including ectopic pregnancy, infertility, and adverse pregnancy outcomes. Mouse models of infection suggest that chlamydia\n                  <jats:italic>-<\/jats:italic>\n                  induced dysregulation of microRNAs (miRNAs) can drive harmful cytokine responses, pathogenic epithelial-mesenchymal transition (EMT), and fibrosis. To investigate these mechanisms in humans, we profiled miRNA and mRNA expression in endometrial biopsies from women with endometrial infection (Endo+) and compared them to profiles from women with cervix-only infection (Endo-) or no infection. Ingenuity Pathway Analysis (IPA) revealed that Endo+ tissues had upregulated genes associated with innate and adaptive immune response pathways, as well as EMT regulation, while downregulated genes were linked to cell cycle control. An integrative miRNA-mRNA analysis, which combined a review of published miRNA regulation in human infections and immune responses with IPA\u2019s miRNA target filter, identified differentially expressed miRNAs that modulate these pathways in the endometrium of Endo+ women. Functional annotation of these miRNAs showed a predominance of downregulated miRNAs that typically suppress EMT and regulatory T cell (Treg) differentiation, along with miRNAs that usually enhance Th17 responses. Comparisons with previously identified mRNA pathways in blood samples from women with endometrial\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  infection indicated that alterations in TGF-\u03b2 signaling and EMT were specific to the endometrium. Overall, the miRNA-mRNA interactions inferred from Endo+ tissue suggest increased activity in TGF-\u03b2 pathways that promote enhanced EMT and Treg differentiation, while reducing Th17 activation. These changes highlight a dual potential for promoting tissue scarring while dampening inflammatory responses that could otherwise limit infection.\n                <\/jats:p>","DOI":"10.1101\/2025.06.23.661210","type":"posted-content","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T11:55:16Z","timestamp":1750938916000},"source":"Crossref","is-referenced-by-count":0,"title":["miRNA\/mRNA analysis of increased TGF-\u03b2 pathways drive epithelial-mesenchymal transition and regulatory T cell differentiation"],"prefix":"10.64898","author":[{"given":"Toni","family":"Darville","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-684X","authenticated-orcid":false,"given":"Catherine M.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Mokashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"},{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9026-707X","authenticated-orcid":false,"given":"Weiming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles W.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Pathology consultant, Newburyport, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Weisenfeld","sequence":"additional","affiliation":[{"name":"The University of Pittsburgh School of Medicine and the Magee-Womens Research Institute, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC"},{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041210213761000_2025.06.23.661210v2.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03440230060033"},{"key":"2026041210213761000_2025.06.23.661210v2.2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-1748023"},{"key":"2026041210213761000_2025.06.23.661210v2.3","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2019-053999"},{"key":"2026041210213761000_2025.06.23.661210v2.4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01023"},{"key":"2026041210213761000_2025.06.23.661210v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.06.013"},{"key":"2026041210213761000_2025.06.23.661210v2.6","doi-asserted-by":"crossref","unstructured":"Stary, G. , A. 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