Interaction of RAS activation and lipid disorders accelerates the progression of glomerulosclerosis.
Interaction of RAS activation and lipid disorders accelerates the progression of glomerulosclerosis.
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DOI：
10.7150/ijms.6635
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发表时间：
2013
影响因子：
3.6
通讯作者：
Liu BC
中科院分区：
文献类型：
--
作者：
Ma KL;Ni J;Wang CX;Liu J;Zhang Y;Wu Y;Lv LL;Ruan XZ;Liu BC
背景：肾素-血管紧张素系统（RAS）的激活和脂质紊乱是进展性慢性肾脏病的主要危险因素。本研究旨在探讨RAS激活和脂质紊乱导致肾小球硬化的潜在协同机制。材料与方法：用10-7 mol/L血管紧张素Ⅱ（Ang Ⅱ）或30 μg/ml胆固醇和1 μg/ml 25-羟基胆固醇（脂质负荷）处理人肾小球系膜细胞（HMCs）24小时。通过油红O染色和细胞内胆固醇定量测定来评估细胞中的脂质积累。通过实时聚合酶链反应和蛋白质印迹法检测低密度脂蛋白受体（LDLr）通路、RAS家族和细胞外基质中分子的基因和蛋白质表达。固醇调节元件结合蛋白（SREBP）裂解激活蛋白（SCAP）的易位，护送SREBP-2从内质网（ER）到高尔基体，通过免疫荧光染色检查。结果：Ang Ⅱ可增加HMCs内脂滴的积聚。进一步分析表明，Ang II增加了LDLr、SCAP和SREBP-2的mRNA和蛋白表达。这种增加与血管紧张素II诱导的HMCs中SCAP/SREBP-2复合物从ER到高尔基体的增强易位相关，从而激活LDLr基因转录。有趣的是，脂质负荷增加血管紧张素原、血管紧张素II、肾素、血管紧张素转换酶、血管紧张素II 1型受体和2型受体的mRNA和蛋白表达，同时增加I型胶原、α-平滑肌肌动蛋白和纤连蛋白的mRNA和蛋白表达。结论：本研究表明，RAS激活和脂质紊乱的相互作用加速肾小球硬化的进展。
Background: The activation of the renin-angiotensin system (RAS) and lipid disorders are major risk factors in progressive chronic kidney disease. This study aimed to investigate the potential synergistic mechanisms of RAS activation and lipid disorders that contribute to glomerulosclerosis. Materials and methods: Human renal mesangial cells (HMCs) were treated with 10-7 mol/L angiotensin II (Ang II) or with 30 μg/ml cholesterol and 1 μg/ml 25-hydroxycholesterol (lipid loading) for 24 hours. Lipid accumulation in the cells was evaluated by Oil Red O staining and intracellular cholesterol quantitative assays. The gene and protein expression of molecules in the low-density lipoprotein receptor (LDLr) pathway, the RAS family, and the extracellular matrix were examined by real-time polymerase chain reaction and Western blotting. The translocation of sterol regulatory element-binding protein (SREBP) cleavage activating protein (SCAP), which escorts SREBP-2 from the endoplasmic reticulum (ER) to the Golgi, was examined by immunofluorescent staining. Results: Ang II increased lipid droplet accumulation in HMCs. Further analysis revealed that Ang II increased the mRNA and protein expression of LDLr, SCAP, and SREBP-2. This increase was correlated with an enhanced translocation of the SCAP/SREBP-2 complex from the ER to the Golgi in HMCs that was induced by Ang II, thereby activating LDLr gene transcription. Interestingly, lipid loading increased the mRNA and protein expression of angiotensinogen, Ang II, renin, angiotensin-converting enzyme, angiotensin II type 1 receptor, and type 2 receptor in HMCs with increased mRNA and protein expression of collagen I, α-smooth muscle actin, and fibronectin. Conclusions: This study demonstrates that the interaction of RAS activation and lipid disorders accelerates the progression of glomerulosclerosis.
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影响因子：
8.3
作者：
Saito, K;Ishizaka, N;Nagai, R
通讯作者：
Nagai, R
DOI：
10.1111/j.1559-4572.2008.00052.x
发表时间：
2009-01-01
期刊：
Journal of the cardiometabolic syndrome
影响因子：
--
作者：
Kostapanos, Michael S;Liberopoulos, Evangelos N;Elisaf, Moses S
通讯作者：
Elisaf, Moses S
DOI：
10.1152/ajprenal.00160.2003
发表时间：
2003-11-01
影响因子：
4.2
作者：
Park, SY;Song, CY;Lee, HS
通讯作者：
Lee, HS
影响因子：
2.2
作者：
Catar, R. A.;Mueller, G.;Morawietz, H.
通讯作者：
Morawietz, H.
影响因子：
3.4
作者：
Wang X;Phillips MI;Mehta JL
通讯作者：
Mehta JL