{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:34:18Z","timestamp":1780047258418,"version":"3.53.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The present study was funded by the Key Scientific Project of the Affiliated Hospital of North Sichuan Medical College","award":["19ZD004"],"award-info":[{"award-number":["19ZD004"]}]},{"name":"the Scientific and Technological Cooperation Project of Nanchong City","award":["18SXHZ0577"],"award-info":[{"award-number":["18SXHZ0577"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The estrogen inhibits colonic smooth muscle contractions, which may lead to constipation. However, the mechanisms of inhibition are poorly understood. Therefore, the present study examined the effect of estrogen on rat colonic smooth muscle contractions and its potential association with the large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup> channels \u03b21 (BK\u03b21) subunit. Twenty-four female Sprague Dawley rats were randomly assigned to 4 groups. After 2 weeks of intervention, the contraction activity of isolated colonic smooth muscle and the expression of BK\u03b21 in colonic smooth muscle of rats were detected. Additionally, in order to investigate the effects of estrogen on BK\u03b21 expression and calcium mobilization, in vitro experiments were conducted using rat and human colonic smooth muscle cells (SMCs). BK\u03b21 shRNA was used to investigate whether calcium mobilization is affected by BK\u03b21 in colonic SMCs. To explore the relationship between ER\u03b2 and BK\u03b21, serial deletions, site-directed mutagenesis, a dual-luciferase reporter assay, and chromatin immunoprecipitation assays were employed. In response to E2, colonic smooth muscle strips showed a decrease in tension, while IBTX exposure transiently increased tension. Furthermore, in these muscle tissues, BK\u03b21 and \u03b1-SMA were found to be co-expressed. The E2 group showed significantly higher BK\u03b21 expression. In cultured colonic SMCs, the expression of BK\u03b21 was found to increase in the presence of E2 or DPN. E2 treatment reduced Ca<jats:sup>2+<\/jats:sup> concentrations, while BK\u03b21 shRNA treatment increased Ca<jats:sup>2+<\/jats:sup> concentrations relative to the control. ER\u03b2-initiated BK\u03b21 expression appears to occur via binding to the BK\u03b21 promoter. These results indicated that E2 may upregulate BK\u03b21 expression via ER\u03b2 and inhibit colonic smooth muscle contraction through ER\u03b2 by directly targeting BK\u03b21.<\/jats:p>","DOI":"10.1371\/journal.pone.0294249","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T18:31:46Z","timestamp":1699641106000},"page":"e0294249","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Estrogen inhibits colonic smooth muscle contractions by regulating BK\u03b21 signaling"],"prefix":"10.1371","volume":"18","author":[{"given":"Jing","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peidong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaihua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-638X","authenticated-orcid":true,"given":"Guangjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"pone.0294249.ref001","doi-asserted-by":"crossref","first-page":"17095","DOI":"10.1038\/nrdp.2017.95","article-title":"Chronic 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