Abstract:
: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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Liu L,Mao L,Xu Y,Wu Xdoi
10.1016/j.bbrc.2019.07.077subject
Has Abstractpub_date
2019-09-17 00:00:00pages
244-252issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(19)31431-7journal_volume
517pub_type
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