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We aimed to study the role of the pro\u2010ANP convertase Corin in the pathogenesis of DN. Corin and ANP expression in DN rat kidneys and high\u2010glucose\u2010treated HK\u20102 cells was analyzed by real\u2010time PCR, western blotting, and immunohistochemical staining. The effect of Corin\u2010siRNA or ANP\u2010siRNA HK\u20102 cells on EA.hy926 cell migration was determined by scratch\u2010wound healing assay. The expression of mitogen\u2010activated protein kinase (MAPK) and endothelial NO synthase (eNOS) in EA.hy926 cells treated with conditioned medium from Corin\u2010siRNA\u2010 or ANP\u2010siRNA\u2010transfected HK\u20102 cells was determined by western blotting. We found a significant reduction in Corin and ANP expression in DN rat kidneys. These results were recapitulated in HK\u20102 cells treated with high glucose. EA.hy926 cells treated with conditioned medium from Corin\u2010deficient HK\u20102 cells had inhibited migration, increased MAPK activity, and decreased eNOS activity. Similar effects were observed with ANP\u2010siRNA transfection. Finally, adding ANP to the Corin\u2010deficient HK\u20102 conditioned medium rescued the above defects, indicating that Corin mediates its effects through ANP. In conclusion, Corin plays a renoprotective role through pro\u2010ANP processing, and defects in Corin cause endothelial dysfunction through MAPK and eNOS signaling in DN.<\/jats:p>","DOI":"10.1096\/fj.201900531rr","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T12:08:20Z","timestamp":1574165300000},"page":"95-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Corin plays a protective role via upregulating MAPK and downregulating eNOS in diabetic nephropathy endothelial dysfunction"],"prefix":"10.1096","volume":"34","author":[{"given":"Meiting","family":"Xue","sequence":"first","affiliation":[{"name":"School of Medical Laboratory Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Cancer Prevention and Therapy National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin China"},{"name":"Key Laboratory of 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