Dorotea Debra, Koya Daisuke, Ha Hunjoo
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Front Pharmacol. 2020 Mar 17;11:265. doi: 10.3389/fphar.2020.00265. eCollection 2020.
Sterol regulatory-element binding proteins (SREBPs) are classical regulators of cellular lipid metabolism in the kidney and other tissues. SREBPs are currently recognized as versatile transcription factors involved in a myriad of cellular processes. Meanwhile, SREBPs have been recognized to mediate lipotoxicity, contributing to the progression of kidney diseases. SREBP1 has been shown to bind to the promoter region of TGFβ, a major pro-fibrotic signaling mechanism in the kidney. Conversely, TGFβ activates SREBP1 transcriptional activity suggesting a positive feedback loop of SREBP1 in TGFβ signaling. Public ChIP-seq data revealed numerous non-lipid transcriptional targets of SREBPs that plausibly play roles in progressive kidney disease and fibrosis. This review provides new insights into SREBP as a mediator of kidney fibrosis via lipid-independent pathways.
固醇调节元件结合蛋白(SREBPs)是肾脏和其他组织中细胞脂质代谢的经典调节因子。SREBPs目前被认为是参与众多细胞过程的多功能转录因子。与此同时,SREBPs已被认为可介导脂毒性,促进肾脏疾病的进展。SREBP1已被证明可与TGFβ的启动子区域结合,TGFβ是肾脏中主要的促纤维化信号机制。相反,TGFβ激活SREBP1的转录活性,表明SREBP1在TGFβ信号传导中存在正反馈回路。公开的染色质免疫沉淀测序(ChIP-seq)数据揭示了SREBPs的众多非脂质转录靶点,这些靶点可能在进行性肾脏疾病和纤维化中发挥作用。本综述通过脂质非依赖途径为SREBP作为肾脏纤维化介质提供了新的见解。