{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:14:18Z","timestamp":1790316858192,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,1]]},"abstract":"\n Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein\u2013coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G\u2013protein\n \u03b2\u03b3<\/jats:italic>\n \u2013subunit (G\n \u03b2\u03b3<\/jats:italic>\n ), GPCR-kinase 2, and\n \u03b2<\/jats:italic>\n -arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR\u2013G\n \u03b2\u03b3<\/jats:italic>\n inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR\u2013G\n \u03b2\u03b3<\/jats:italic>\n signaling and ET system expression. Notably, systemic pharmacologic G\n \u03b2\u03b3<\/jats:italic>\n inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore,\n in vitro<\/jats:italic>\n studies showed a key role for ET receptor\u2013G\n \u03b2\u03b3<\/jats:italic>\n signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-G\n \u03b2\u03b3<\/jats:italic>\n in AKI and suggest GPCR-G\n \u03b2\u03b3<\/jats:italic>\n inhibition as a novel therapeutic approach for treating CRS2 and AKI.\n <\/jats:p>","DOI":"10.1681\/asn.2015080852","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T23:05:35Z","timestamp":1465859135000},"page":"197-208","source":"Crossref","is-referenced-by-count":46,"title":["G Protein\u2013Coupled Receptor-G\u2013Protein \u03b2\u03b3\u2013Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure"],"prefix":"10.1681","volume":"28","author":[{"given":"Fadia A.","family":"Kamal","sequence":"first","affiliation":[{"name":"The Heart Institute, Molecular Cardiovascular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua G.","family":"Travers","sequence":"additional","affiliation":[{"name":"The Heart Institute, Molecular Cardiovascular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison E.","family":"Schafer","sequence":"additional","affiliation":[{"name":"The Heart Institute, Molecular Cardiovascular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad","family":"Devarajan","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burns C.","family":"Blaxall","sequence":"additional","affiliation":[{"name":"The Heart Institute, Molecular Cardiovascular Biology 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