{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:47:12Z","timestamp":1789447632135,"version":"build-2803163510"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ20H270019"],"award-info":[{"award-number":["LQ20H270019"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY17H040004"],"award-info":[{"award-number":["LY17H040004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical and health science and technology program of Zhejiang Province","award":["2021KY767"],"award-info":[{"award-number":["2021KY767"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500061"],"award-info":[{"award-number":["81500061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Stress urinary incontinence (SUI) is a common condition in women and associated with extra-cellular matrix (ECM) reconstruction, which is mainly regulated by fibroblasts. However, the underlying mechanism remains obscure. Small extracellular vesicles (sEVs) play fundamental biological roles in various cellular functions. Some studies suggested that the sEVs were involved in the metabolism of ECM and the function of fibroblasts. The purpose of our study was to investigate the effect of sEVs secreted by vaginal fibroblasts on the pathogenesis of SUI. We showed that the fibroblasts of female anterior vaginal wall secreted sEVs. Moreover, fibroblasts of females with SUI had significantly elevated secretion of sEVs. The collagen contents, proliferation and migration capacity of fibroblasts were decreased when fibroblasts were co-cultured with fibroblasts-derived sEVs (fibroblast-sEVs) from SUI patients. Proteomic analysis revealed that fibroblast-sEVs contained various differentially expressed proteins including TIMP2, TGF-\u03b2 and ABCC4, which were involved in signaling pathways of fibroblasts regulation. Therefore, we suggested that fibroblast-sEVs contributed to the pathogenesis of SUI through various proteins including TIMP2, TGF-\u03b2 and ABCC4.<\/jats:p>","DOI":"10.1371\/journal.pone.0249977","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T17:34:44Z","timestamp":1617989684000},"page":"e0249977","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Small extracellular vesicles secreted by vaginal fibroblasts exert inhibitory effect in female stress urinary incontinence through regulating the function of fibroblasts"],"prefix":"10.1371","volume":"16","author":[{"given":"Xiaoyan","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-390X","authenticated-orcid":true,"given":"Zhenwei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"pone.0249977.ref001","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s11934-011-0206-0","article-title":"Epidemiology of stress urinary incontinence in women","volume":"12","author":"WS Reynolds","year":"2011","journal-title":"Curr Urol Rep"},{"key":"pone.0249977.ref002","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s001920070021","article-title":"Epidemiology and natural history of urinary incontinence","volume":"11","author":"S Hunskaar","year":"2000","journal-title":"Int Urogynecol J"},{"key":"pone.0249977.ref003","doi-asserted-by":"crossref","first-page":"8524353","DOI":"10.1155\/2017\/8524353","article-title":"Mechanism of Mechanical Trauma-Induced Extracellular Matrix Remodeling of Fibroblasts in Association with Nrf2\/ARE Signaling Suppression Mediating TGF-beta1\/Smad3 Signaling Inhibition","volume":"2017","author":"J Tang","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0249977.ref004","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cellsig.2019.03.023","article-title":"Electrical stimulation activates calpain 2 and subsequently upregulates collagens via the integrin beta 1\/TGF-beta 1 signaling pathway","volume":"59","author":"Y Li","year":"2019","journal-title":"Cell Signal"},{"key":"pone.0249977.ref005","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/bju.12819","article-title":"The scientific basis for the use of biomaterials in stress urinary incontinence (SUI) and pelvic organ prolapse (POP)","volume":"115","author":"M Colaco","year":"2015","journal-title":"Bju Int"},{"key":"pone.0249977.ref006","doi-asserted-by":"crossref","first-page":"22971","DOI":"10.1038\/srep22971","article-title":"Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content","volume":"6","author":"AM Ruiz-Zapata","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0249977.ref007","first-page":"474","article-title":"Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial (vol 369, pg 2179, 2007)","volume":"371","author":"H Strasser","year":"2008","journal-title":"Lancet"},{"key":"pone.0249977.ref008","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1016\/S0140-6736(07)60990-8","article-title":"Myoblasts and fibroblasts in stress urinary incontinence","volume":"369","author":"G Novara","year":"2007","journal-title":"Lancet"},{"key":"pone.0249977.ref009","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"C Th\u00e9ry","year":"2018","journal-title":"Journal of Extracellular Vesicles"},{"key":"pone.0249977.ref010","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"G van Niel","year":"2018","journal-title":"Nature reviews. 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