长链非编码 RNA MALAT1 与转录因子 Foxo1 相互作用，调节高糖诱导的 HK-2 细胞损伤中的 SIRT1 转录。
Long non-coding RNA MALAT1 interacts with transcription factor Foxo1 to regulate SIRT1 transcription in high glucose-induced HK-2 cells injury.
机构信息
Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
出版信息
Biochem Biophys Res Commun. 2018 Sep 5;503(2):849-855. doi: 10.1016/j.bbrc.2018.06.086. Epub 2018 Jul 14.
BACKGROUND
Tubular injury is considered as a crucial pathological feature of diabetic nephropathy. LncRNA MALAT1 is involved in diabetic complications. Hence the role of MALAT1 in high glucose-induced renal tubular epithelial cells (HK-2) injury deserves investigation.
METHODS
The diabetic mice model was established with streptozotocin (STZ) injection. The expression of NEAT1, SIRT1, and Foxo1 mRNA and protein was determined with qRT-PCR and western blot, respectively. The serum creatinine and urinary albumin were examined by enzyme linked immunosorbent assay (ELISA). Interaction between MALAT1 and Foxo1 was detected with RIP and RNA pull-down assay, respectively. Dual luciferase reporter assay was used to evaluate the binding between Foxo1 and SIRT1.
RESULTS
LncRNA MALAT1 was up-regulated in kidney tissues of diabetic mice and in HK-2 cells treated with high glucose, while the expression of SIRT1 was decreased. Interaction between MALAT1 and Foxo1 was observed in HK-2 cells and the interaction was promoted by high glucose treatment. Foxo1 activated SIRT1 transcription by binding to its promoter, and MALAT1 repressed SIRT1 expression through targeting Foxo1.
CONCLUSION
LncRNA MALAT1 interacts with transcription factor Foxo1 to represses SIRT1 transcription in high glucose incubated HK-2 cells, which promotes high glucose-induced HK-2 cells injury.
背景
管状损伤被认为是糖尿病肾病的关键病理特征。LncRNA MALAT1 参与糖尿病并发症。因此，MALAT1 在高糖诱导的肾小管上皮细胞（HK-2）损伤中的作用值得研究。
方法
通过链脲佐菌素（STZ）注射建立糖尿病小鼠模型。分别通过 qRT-PCR 和 Western blot 测定 NEAT1、SIRT1 和 Foxo1 mRNA 和蛋白的表达。通过酶联免疫吸附试验（ELISA）检测血清肌酐和尿白蛋白。分别通过 RIP 和 RNA 下拉测定检测 MALAT1 和 Foxo1 之间的相互作用。双荧光素酶报告基因测定用于评估 Foxo1 和 SIRT1 之间的结合。
结果
LncRNA MALAT1 在糖尿病小鼠肾脏组织和高糖处理的 HK-2 细胞中上调，而 SIRT1 的表达降低。在 HK-2 细胞中观察到 MALAT1 与 Foxo1 之间的相互作用，并且高糖处理促进了这种相互作用。Foxo1 通过结合其启动子激活 SIRT1 转录，而 MALAT1 通过靶向 Foxo1 抑制 SIRT1 表达。
结论
LncRNA MALAT1 与转录因子 Foxo1 相互作用，抑制高糖孵育的 HK-2 细胞中 SIRT1 的转录，从而促进高糖诱导的 HK-2 细胞损伤。
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