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Publication : Endothelial-specific deletion of Brahma-related gene 1 (BRG1) assuages unilateral ureteral obstruction induced renal injury in mice.

First Author  Liu L Year  2019
Journal  Biochem Biophys Res Commun Volume  517
Issue  2 Pages  244-252
PubMed ID  31349970 Mgi Jnum  J:291670
Mgi Id  MGI:6443102 Doi  10.1016/j.bbrc.2019.07.077
Citation  Liu L, et al. (2019) Endothelial-specific deletion of Brahma-related gene 1 (BRG1) assuages unilateral ureteral obstruction induced renal injury in mice. Biochem Biophys Res Commun 517(2):244-252
abstractText  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.
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