Life Sciences ( IF 6.1 ) Pub Date : 2020-11-21 , DOI: 10.1016/j.lfs.2020.118794 Hu Zhang 1 , Yu Yan 1 , Qingfeng Hu 2 , Xiaohui Zhang 3
Objective
The abnormal expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) has been demonstrated to exert pivotal effects in human diseases. We focused on the functions of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA let-7f on diabetic nephropathy (DN).
Methods
The diabetes (db/db) mice were treated with silenced MALAT1, then the baseline indicators, pathology changes, marker proteins of podocyte injury (nephrin, podocin, desmin and Cleaved caspase-3), oxidative stress indicators and inflammatory factors in renal tissues were determined. Murine podocyte MPC5 cells were stimulated by high glucose (HG) and transfected with sh-MALAT1 or let-7f mimic, then the cell migration, adhesion ability and apoptosis were evaluated. Moreover, the binding relationship between MALAT1 and let-7f, and the targeting relationship between let-7f and krüppel-like factor 5 (KLF5) were confirmed.
Results
Silenced MALAT1 could improve baseline indicators of DN mice, and also improved pathology, increased nephrin and podocin expression, decreased desmin and Cleaved caspase-3 expression, and restrained oxidative stress and inflammatory reaction in their renal tissues. Additionally, elevated let-7f and reduced MALAT1 could restrict migration and apoptosis of HG-induced MPC5 cells, and promoted the cell adhesion ability.
Conclusion
Results in our research indicated that the reduced MALAT1 could relieve the podocyte injury in DN by upregulating let-7f and inhibiting KLF5, which may be helpful for DN therapy.
中文翻译:
LncRNA MALAT1/microRNA let-7f/KLF5轴调控糖尿病肾病足细胞损伤
客观的
microRNA (miRNA) 和长链非编码 RNA (lncRNA) 的异常表达已被证明在人类疾病中发挥关键作用。我们专注于转移相关肺腺癌转录本 1 (MALAT1) 和 microRNA let-7f 在糖尿病肾病 (DN) 中的功能。
方法
糖尿病(db/db)小鼠经沉默MALAT1处理后,比较基线指标、病理变化、足细胞损伤标志蛋白(nephrin、podocin、desmin和Cleaved caspase-3)、氧化应激指标和肾组织炎症因子。决定。小鼠足细胞MPC5细胞经高糖(HG)刺激后转染sh-MALAT1或let-7f mimic,然后评估细胞迁移、粘附能力和凋亡。此外,确认了 MALAT1 和 let-7f 之间的结合关系,以及 let-7f 和 krüppel 样因子 5 (KLF5) 之间的靶向关系。
结果
沉默的 MALAT1 可以改善 DN 小鼠的基线指标,还可以改善病理学,增加 nephrin 和 podocin 的表达,降低结蛋白和 Cleaved caspase-3 的表达,抑制肾组织的氧化应激和炎症反应。此外,升高的 let-7f 和降低的 MALAT1 可以限制 HG 诱导的 MPC5 细胞的迁移和凋亡,并促进细胞粘附能力。
结论
我们的研究结果表明,减少的 MALAT1 可以通过上调 let-7f 和抑制 KLF5 来减轻 DN 的足细胞损伤,这可能有助于 DN 的治疗。