Endothelial-specific deletion of Brahma-related gene 1 (BRG1) assuages unilateral ureteral obstruction induced renal injury in mice.
Endothelial-specific deletion of Brahma-related gene 1 (BRG1) assuages unilateral ureteral obstruction induced renal injury in mice.
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DOI：
10.1016/j.bbrc.2019.07.077
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发表时间：
2019-09
影响因子：
3.1
通讯作者：
Li Liu;L. Mao;Yong Xu;Xiaoyan Wu
中科院分区：
文献类型：
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作者：
Li Liu;L. Mao;Yong Xu;Xiaoyan Wu
肾脏稳态是由肾脏中不同细胞类型（包括内皮细胞）之间的相互作用调节的。在本研究中，我们研究了阻塞性肾病（ON）小鼠模型中BRG 1（一种染色质重塑蛋白）对内皮细胞表型的调节。我们报告，内皮特异性删除BRG1减弱单侧输尿管梗阻（UUO）诱导的小鼠肾脏炎症，证明了下调促炎细胞因子和减少免疫细胞浸润。此外，内皮BRG1缺陷抑制UUO诱导的小鼠肾纤维化，通过促纤维化基因的表达，胶原组织的天狼星红染色和羟脯氨酸水平的定量来测量。BRG 1通过募集组蛋白修饰酶激活内皮细胞中粘附分子和趋化因子的转录，从而导致巨噬细胞粘附和趋化。总之，我们认为BRG 1对内皮功能的表观遗传调节可能在ON发病机制中发挥积极作用。
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.