长链非编码 RNA MALAT1 通过 p38MAPK 通路促进糖尿病性白内障中人晶状体上皮细胞的凋亡和氧化应激。
LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract.
机构信息
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Ophthalmology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
出版信息
Diabetes Res Clin Pract. 2018 Oct;144:314-321. doi: 10.1016/j.diabres.2018.06.020. Epub 2018 Jun 22.
BACKGROUND
LncRNAs are involved in various biological processes and disorders. We aimed to investigate the role of lncRNA MALAT1 deregulation in the pathogenic mechanism of diabetic cataract (DC).
METHODS
The expression of MALAT1 in the tissues and cells was detected by qRT-PCR. The levels of SP1, p38 and apoptosis-related protein were assessed by Western blot assay. Chromatin immunoprecipitation assay and Dual luciferase assay were performed to evaluate the relationship between SP1 and MALAT1. The viability and apoptosis of human lens epithelial cells (HLECs) were analyzed by MTT assay and flow cytometry. The levels of malonyldialdehyde (MDA), superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px) were used to examine the level of oxidative stress.
RESULTS
MALAT1 not only was aberrantly expressed in DC anterior lens capsule tissues and high glucose (HG)-treated HLECs, but also were up-regulated by HG to promote the apoptosis and oxidative stress of HLECs. HG induced the up-regulation of MALAT1 via SP1 binding MALAT1 promoter regions in HLECs. Moreover, p38 was up-regulated in HG-treated HLECs, and knockdown of p38 reversed the effect of MALAT1 over-expression on HLECs.
CONCLUSION
HG induced the up-regulation of MALAT1 in HLECs via SP1 binding SP1 binding MALAT1, which promoted the apoptosis and oxidative stress of HLECs through the activation of p38MAPK signaling pathway.
背景
长链非编码 RNA（lncRNA）参与多种生物过程和疾病。我们旨在研究 lncRNA MALAT1 失调在糖尿病性白内障（DC）发病机制中的作用。
方法
通过 qRT-PCR 检测 MALAT1 在组织和细胞中的表达。通过 Western blot 检测 SP1、p38 和凋亡相关蛋白的水平。通过染色质免疫沉淀测定和双荧光素酶测定评估 SP1 和 MALAT1 之间的关系。通过 MTT 测定和流式细胞术分析人晶状体上皮细胞（HLEC）的活力和凋亡。通过丙二醛（MDA）、超氧化物歧化酶（SOD）和磷脂氢过氧化物谷胱甘肽过氧化物酶（GSH-Px）水平检测氧化应激水平。
结果
MALAT1 在 DC 前晶状体囊组织和高糖（HG）处理的 HLEC 中不仅异常表达，而且被 HG 上调以促进 HLEC 的凋亡和氧化应激。HG 通过 SP1 结合 HLEC 中 MALAT1 启动子区域诱导 MALAT1 的上调。此外，p38 在 HG 处理的 HLEC 中上调，并且 p38 的敲低逆转了 MALAT1 过表达对 HLEC 的影响。
结论
HG 通过 SP1 结合 MALAT1 诱导 HLEC 中 MALAT1 的上调，通过激活 p38MAPK 信号通路促进 HLEC 的凋亡和氧化应激。
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