{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:06Z","timestamp":1787028486986,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development of China","doi-asserted-by":"publisher","award":["2018YFC1004800"],"award-info":[{"award-number":["2018YFC1004800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development of China","doi-asserted-by":"publisher","award":["81571414"],"award-info":[{"award-number":["81571414"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development of China","doi-asserted-by":"publisher","award":["ZR2019PH022"],"award-info":[{"award-number":["ZR2019PH022"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development of China","doi-asserted-by":"publisher","award":["2020ZLYS02"],"award-info":[{"award-number":["2020ZLYS02"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018YFC1004800"],"award-info":[{"award-number":["2018YFC1004800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571414"],"award-info":[{"award-number":["81571414"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZR2019PH022"],"award-info":[{"award-number":["ZR2019PH022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020ZLYS02"],"award-info":[{"award-number":["2020ZLYS02"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Shandong Province","award":["2018YFC1004800"],"award-info":[{"award-number":["2018YFC1004800"]}]},{"name":"Natural Science Foundation of Shandong Province","award":["81571414"],"award-info":[{"award-number":["81571414"]}]},{"name":"Natural Science Foundation of Shandong Province","award":["ZR2019PH022"],"award-info":[{"award-number":["ZR2019PH022"]}]},{"name":"Natural Science Foundation of Shandong Province","award":["2020ZLYS02"],"award-info":[{"award-number":["2020ZLYS02"]}]},{"name":"Shandong Provincial Key Research and Development Program","award":["2018YFC1004800"],"award-info":[{"award-number":["2018YFC1004800"]}]},{"name":"Shandong Provincial Key Research and Development Program","award":["81571414"],"award-info":[{"award-number":["81571414"]}]},{"name":"Shandong Provincial Key Research and Development Program","award":["ZR2019PH022"],"award-info":[{"award-number":["ZR2019PH022"]}]},{"name":"Shandong Provincial Key Research and Development Program","award":["2020ZLYS02"],"award-info":[{"award-number":["2020ZLYS02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intrauterine adhesion (IUA) refers to injury to the basal layer of the endometrium, which can be caused by various factors. It is often accompanied by clinical symptoms such as abnormal menstruation, infertility, recurrent abortion, and periodic abdominal pain. In recent years, a number of studies have reported the effects of \u03b2-Klotho (KLB) on the occurrence and development of human tumors and fibrotic diseases, but its relationship with endometrial fibroblasts and endometrial fibrosis has not been elucidated. In this study, we compared the expression of KLB in endometrial stromal cells (ESCs) from patients with IUA and normal controls. We constructed animal and cell models of IUA and conducted expression verification and functional experiments on KLB. We found that the expression of KLB was significantly increased in the ESCs of IUA patients and rat models compared with the controls. The overexpression of KLB could promote the proliferation and fibrosis of ESCs. In addition, the overexpression of KLB activated the PI3K\/AKT signaling pathway in ESCs. Our study shows that KLB protein is highly expressed in the ESCs of patients with IUA and can enhance stromal cell proliferation and cell fibrosis by activating the PI3K\/AKT pathway, thus promoting the development of IUA.<\/jats:p>","DOI":"10.3390\/ijms231911294","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["\u03b2-Klotho Promotes the Development of Intrauterine Adhesions via the PI3K\/AKT Signaling Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Zizhen","family":"Guo","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan 250000, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250000, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan 250000, China"},{"name":"The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, China"},{"name":"Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan 250000, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250000, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan 250000, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250000, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan 250000, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250000, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.fertnstert.2008.02.096","article-title":"Asherman syndrome\u2014One century later","volume":"89","author":"Yu","year":"2008","journal-title":"Fertil Steril"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0015-0282(16)46268-0","article-title":"Intrauterine adhesions: An updated appraisal","volume":"37","author":"Schenker","year":"1982","journal-title":"Fertil Steril"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jmig.2016.09.022","article-title":"Prevalence and Impact of Chronic Endometritis in Patients With Intrauterine Adhesions: A Prospective Cohort Study","volume":"24","author":"Chen","year":"2017","journal-title":"J. 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