화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.517, No.2, 244-252, 2019
Endothelial-specific deletion of Brahma-related gene 1 (BRG1) assuages unilateral ureteral obstruction induced renal injury in mice
Renal homeostasis is regulated by the interplay among different cell types in the kidneys including endothelial cells. In the present study we investigated the phenotypic regulation of endothelial cells by BRG1, a chromatin remodeling protein, in a mouse model of obstructive nephropathy (ON). We report that endothelial-specific deletion of BRG1 attenuated renal inflammation induced by unilateral ureteral tract obstruction (UUO) in mice, as evidenced by down-regulation of pro-inflammatory cytokines and diminished infiltration of immune cells. Moreover, endothelial BRG1 deficiency suppressed UUO-induced renal fibrosis in mice as measured by expression of pro-fibrogenic genes, picrosirius red staining of collagenous tissues, and quantification of hydroxylproline levels. Mechanistically, BRG1 activated the transcription of adhesion molecules and chemokines in endothelial cells by recruiting histone modifying enzymes leading to macrophage adhesion and chemotaxis. In conclusion, we propose that epigenetic regulation of endothelial function by BRG1 may play an active role in ON pathogenesis. (C) 2019 Elsevier Inc. All rights reserved.