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In the present study, we performed label\u2010free proteomics using placentas from GDM patients and normal controls. Vitronectin caused our attention among differentially expressed proteins due to its potential role in the pathological progression of GDM. Vitronectin was increased in the placentas of GDM patients, which was confirmed by Western blot analysis. Vitronectin represses insulin signal transduction in trophoblast cells, whereas the knockdown of vitronectin further potentiates insulin\u2010evoked events. Neutralization of CD51\/61 abolishes the repressed insulin signal transduction in vitronectin\u2010treated trophoblast cells. Moreover, vitronectin activates JNK in a CD51\/61\u2010depedent manner. Inhibition of JNK rescues impaired insulin signal transduction induced by vitronectin. Overall, our data indicate that vitronectin binds CD51\/61 in trophoblast cells to activate JNK, and thus induces insulin resistance. In this regard, increased expression of vitronectin is likely a risk factor for the pathological progression of GDM. Moreover, blockade of vitronectin production or its receptors (CD51\/61) may have therapeutic potential for dealing with GDM.<\/jats:p>","DOI":"10.1002\/cbin.12167","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T04:09:51Z","timestamp":1713931791000},"page":"1022-1034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Vitronectin promotes insulin resistance in trophoblast cells by activating JNK in gestational diabetes mellitus"],"prefix":"10.1002","volume":"48","author":[{"given":"Yuejun","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Endocrinology The Second Affiliated Hospital of Soochow University Suzhou Jiangsu P.R. 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