biostudies-literatureMadhusudhan TBMBFDeutscher Akademischer AustauschdienstDFGAlexander von Humboldt-StiftungNational Heart, Lung, and Blood InstituteNHLBI NIH HHSBoehringer IngelheimStiftung Pathobiochemie und Molekulare Diagnostik1762-1780https://www.ebi.ac.uk/biostudies/studies/S-EPMC7460917biostudies-literatureUnknown31(8)<h4>Background</h4>Diabetic nephropathy (dNP), now the leading cause of ESKD, lacks efficient therapies. Coagulation protease-dependent signaling modulates dNP, in part <i>via</i> the G protein-coupled, protease-activated receptors (PARs). Specifically, the cytoprotective protease-activated protein C (aPC) protects from dNP, but the mechanisms are not clear.<h4>Methods</h4>A combination of <i>in vitro</i> approaches and mouse models evaluated the role of aPC-integrin interaction and related signaling in dNP.<h4>Results</h4>The zymogen protein C and aPC bind to podocyte integrin-<i>β</i> ₃, a subunit of integrin-<i>α</i> _v <i>β</i> ₃. Deficiency of this integrin impairs thrombin-mediated generation of aPC on podocytes. The interaction of aPC with integrin-<iJournal of the American Society of Nephrology : JASNPodocyte Integrin-<i>β</i> ₃ and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy.PMC7460917IS-67/11-1C2 SCHA 1082/6-1KO 5736/1-1RTG2408/P5RTG2408/P7RTG2408/P9259130777 – SFB 117701EO1503SFB854/B26236360313 – SFB 1118MO 1082/7-1HL 101917IS-67/8-1R01 HL10191701GM1518ATh1789/1-1WA 3663/2-1Schaefer LRuf WDong WRana RBiemann RMoeller MJGadi IMathew AWang HRezaie ARAl-Dabet MMKrishnan SZeng-Brouwers JGhosh SGupta DZimmermann SReiser JMadhusudhan TElwakiel ANazir SIsermann BStoyanov SKohli SEsmon CTfalsePodocyte Integrin-<i>β</i> ₃ and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy.<h4>Background</h4>Diabetic nephropathy (dNP), now the leading cause of ESKD, lacks efficient therapies. Coagulation protease-dependent signaling modulates dNP, in part <i>via</i> the G protein-coupled, protease-activated receptors (PARs). Specifically, the cytoprotective protease-activated protein C (aPC) protects from dNP, but the mechanisms are not clear.<h4>Methods</h4>A combination of <i>in vitro</i> approaches and mouse models evaluated the role of aPC-integrin interaction and related signaling in dNP.<h4>Results</h4>The zymogen protein C and aPC bind to podocyte integrin-<i>β</i> ₃, a subunit of integrin-<i>α</i> _v <i>β</i> ₃. Deficiency of this integrin impairs thrombin-mediated generation of aPC on podocytes. The interaction of aPC with integrin-<i2020-01-01T00:00:00Z2020 Aug2025-04-04T13:57:20.731Z2022-02-11T00:53:24.814ZS-EPMC74609173270971110.1681/ASN.201911116310.1681/asn.2019111163