Role of the Regulator of G protein Signaling 4 in renal ischemic reperfusion injury and repair
Pang, Paul Daniel
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Regulator of G protein Signaling 4 (RGS4) has previously been shown to prevent prolonged vasoconstriction by binding to the Gq heterodimer. However, the known anti-inflammatory role of RGS4 has not been applied to reperfusion injury in the context of G protein signaling. The aims of this study is to elucidate the expression pattern of RGS4 in renal reperfusion injury to determine if cell signaling initiated by Angiotensin II, a known ligand of Gαq coupled-receptors, is modulated by RGS4. LacZ reporter animals were used to characterize RGS4 expression during reperfusion. Human smooth muscle cells co-cultured with human endothelial cells demonstrated that AngII induces apoptosis in the absence of RGS4 and initiates RANTES expression in smooth muscle cells. SMMHC-Cre rgs4fl/fl confirmed the role of vascular smooth muscle cells to inhibit macrophage localization during reperfusion injury. RGS4 expression in vascular smooth muscle cells therefore inhibits AngII-mediated oxidative stress, leukocyte recruitment by the same cell type, and endothelial damage prior to tubular epithelial injury.
Thesis (M.A.)--Boston University