Angiotensin II induces cholesterol accumulation and injury in podocytes.
Angiotensin II induces cholesterol accumulation and injury in podocytes.
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血管紧张素 II 会诱导足细胞中胆固醇的积累和损伤。
DOI：
10.1038/s41598-017-09733-w
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发表时间：
2017-09-06
影响因子：
4.6
通讯作者：
Ding G
中科院分区：
文献类型：
--
作者：
Yang Y;Yang Q;Yang J;Ma Y;Ding G
血管紧张素II(Ang II)是慢性肾脏疾病(CKD)发生和发展的危险因素，因为Ang II水平升高可导致足细胞损伤。然而，目前还没有关于Ang II在脂代谢中的作用或脂代谢紊乱引起的足细胞损伤的研究。我们的研究表明，血管紧张素Ⅱ诱导足细胞脂滴(LD)积聚和脂滴标志脂肪分化相关蛋白(ADRP)的表达，氯沙坦可减轻脂滴沉积的程度。我们的研究还表明，Ang II增加了足细胞中胆固醇的含量，这是一种LD成分，伴随着这种变化伴随着胆固醇外流相关分子ATP结合盒转运体1(ABCA1)的表达减少，而与胆固醇摄取相关的分子低密度脂蛋白受体(LDLR)和胆固醇合成相关分子固醇调节元件结合蛋白(SREBP1和SREBP2)和3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)的表达增加。甲基-β-环糊精(CD)可诱导胆固醇外流，减少血管紧张素Ⅱ介导的胆固醇蓄积，减少血管紧张素Ⅱ诱导的足细胞凋亡，维持足细胞的骨架和铺展。这些结果提示，Ang II通过调节胆固醇代谢相关分子的表达诱导足细胞胆固醇蓄积，随后的胆固醇代谢障碍导致足细胞损伤。
Angiotensin II (Ang II) is a risk factor for the initiation and progression of chronic kidney disease (CKD), as elevated Ang II levels can lead to podocyte injury. However, there have been no studies on the role of Ang II in lipid metabolism or on podocyte injury caused by lipid dysfunction. Our study showed that Ang II induced lipid droplet (LD) accumulation and expression of the LD marker adipose differentiation-related protein (ADRP) in podocytes, and the extent of lipid deposition could be alleviated by losartan. Our study also demonstrated that Ang II increased the content of cholesterol in podocytes, which is an LD component, and this change was accompanied by decreased expression of the cholesterol efflux-related molecule ATP-binding cassette transporter-1 (ABCA1) and increased expression of the cholesterol uptake-related molecule LDL receptor (LDLR) and the cholesterol synthesis-related molecules sterol regulatory element-binding protein (SREBP1 and SREBP2) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). Pretreating podocytes with methyl-β-cyclodextrin (CD), which induces cholesterol efflux, decreased Ang II-mediated cholesterol accumulation and Ang II-induced podocyte apoptosis and maintained the podocyte cytoskeleton and spreading. These results suggested that Ang II induced podocyte cholesterol accumulation by regulating the expression of cholesterol metabolism-related molecules and that the subsequent cholesterol metabolism dysfunction resulted in podocyte injury.
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