1 alpha,25(OH)(2)D-3 alleviates high glucose-induced lipid accumulation in rat renal tubular epithelial cells by inhibiting SREBPs
1 alpha,25(OH)(2)D-3 alleviates high glucose-induced lipid accumulation in rat renal tubular epithelial cells by inhibiting SREBPs
复制标题
1 alpha,25(OH)(2)D-3 通过抑制 SREBP 减轻高糖诱导的大鼠肾小管上皮细胞脂质积累
DOI：
10.1002/jcb.28786
复制
发表时间：
2019
影响因子：
4
通讯作者：
Zhang Zengli
中科院分区：
文献类型：
--
作者：
Xu Miao;Jiang Fei;Li Bingyan;Zhang Zengli
脂质蓄积是糖尿病肾病进展中的重要事件。1，25-二羟基维生素D3（1α，25（OH）2D 3）被认为对糖尿病肾病有保护作用。然而，1α，25（OH）2D 3是否能抑制脂质蓄积尚不清楚，其可能的机制也不完全清楚。在本研究中，我们评估了1α，25（OH）2D 3对高糖暴露的大鼠肾小管上皮细胞NRK-52 E脂质代谢的影响。结果表明，高糖可促进NRK-52 E细胞的脂质积累，1α，25（OH）2D 3可显著降低高糖诱导的脂质积累。Western blot结果显示，1α，25（OH）2D 3可减轻高糖诱导的固醇调节元件结合蛋白-1c（SREBP-1c）和SREBP 2的表达上调，沿着的还有它们已确定的靶基因脂肪酸合成酶（FATCH）和羟甲基戊二酰辅酶A还原酶（HMGCR）。上述结果提示，1α，25（OH）2D 3通过下调SREBPs的表达抑制高糖诱导的脂质蓄积，为1α，25（OH）2D 3对糖尿病肾病的保护作用提供了新的视角。
Lipid accumulation is a vital event in the progression of diabetic nephropathy. 1,25‐Dihydroxyvitamin D3 (1α,25(OH)2D3) is considered to have a protective effect on diabetic nephropathy. However, it remains unclear whether 1α,25(OH)2D3can inhibit lipid accumulation, and the potential mechanisms responsible for lipid metabolism are incompletely understood. In this study, we evaluated the effects of 1α,25(OH)2D3on lipid metabolism in high glucose–exposed rat renal tubular epithelial NRK‐52E cells. Results indicated that high glucose–enhanced lipid accumulation in NRK‐52E cells and 1α,25(OH)2D3can remarkably decrease high glucose–induced lipid accumulation. Western blot showed that 1α,25(OH)2D3alleviated high glucose–induced upregulation of sterol regulatory element‐binding protein‐1c (SREBP‐1c) and SREBP2, along with their established target genes fatty acid synthase (FASN) and hydroxymethylglutaryl CoA reductases (HMGCR). Overall, these findings suggest that 1α,25(OH)2D3downregulated the expressions of SREBPs to inhibit high glucose–induced lipid accumulation, which provides new sights into the protective effects of 1α,25(OH)2D3on diabetic nephropathy.