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Modulation of integrin function can lead to pathophysiological processes associated with diabetic nephropathy such as alterations in the glomerular filtration barrier and kidney fibrosis. The complexity of these pathophysiological changes implies that multiple integrin subtypes might need to be targeted to ameliorate the progression of renal disease. To address this hypothesis, we investigated the effects of <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20100429, a compound that was originally developed as an <jats:italic>\u03b1<\/jats:italic>v<jats:italic>\u03b2<\/jats:italic>3 inhibitor for the treatment of osteoporosis, on renal function and fibrosis. We demonstrated that <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20100429 is an equipotent pan\u2010inhibitor of multiple <jats:italic>av<\/jats:italic> integrins. <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20100429 dose\u2010dependently inhibited podocyte motility and also suppressed <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010<jats:italic>\u03b2<\/jats:italic>\u2010induced fibrosis marker gene expression in kidney fibroblasts. Moreover, in the obese <jats:styled-content style=\"fixed-case\">ZSF<\/jats:styled-content>1 rat model of diabetic nephropathy, chronic treatment with <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20100429 resulted in significant reduction in proteinuria, kidney fibrosis, and collagen accumulation. In summary, our results suggest that inhibition of multiple integrin subtypes might lead to meaningful impact on proteinuria and renal fibrosis in diabetic nephropathy.<\/jats:p>","DOI":"10.1002\/prp2.354","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T08:36:38Z","timestamp":1505118998000},"source":"Crossref","is-referenced-by-count":48,"title":["An integrin antagonist (<scp>MK<\/scp>\u20100429) decreases proteinuria and renal fibrosis in the <scp>ZSF<\/scp>1 rat diabetic nephropathy model"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5103-783X","authenticated-orcid":false,"given":"Xiaoyan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacology Merck &amp; Co., Inc. 2000 Galloping Hill Road Kenilworth New Jersey 07033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiometabolic Diseases Merck &amp; 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