长链非编码RNA PVT1通过miR-325-3p/Snail1轴调节糖尿病肾病中高糖诱导的细胞活力、氧化应激、纤维化和炎症反应

LncRNA PVT1 Regulates High Glucose-Induced Viability, Oxidative Stress, Fibrosis, and Inflammation in Diabetic Nephropathy via miR-325-3p/Snail1 Axis.

作者信息

Qin Baoyu, Cao Xiaoli

机构信息

Division of Endocrinology and Metabolic, Department of Geriatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Endocrinology, Shanxi Cardiovascular Hospital, Taiyuan, 030024, Shanxi Province, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2021 Apr 19;14:1741-1750. doi: 10.2147/DMSO.S303151. eCollection 2021.

BACKGROUND

Diabetic nephropathy (DN), as a complication of diabetes, is a leading cause of mortality in diabetic patients. It has been reported that lncRNA PVT1 (PVT1) could accelerate the progression of DN by promoting ECM accumulation and increasing the expression of fibronectin 1 (FN1). However, the underlying mechanism of PVT1 on DN remains unknown.

METHODS

To study the effect of PVT1 on DN, mice were injected 50 mg/kg STZ to build the DN models. Mesangial cells (MCs) were induced by high glucose as in vitro model of DN. The expression level of PVT1, miR-325-3 and Snail1 was assessed by qRT-PCR and Western blot. Luciferase reporter assay, RNA pull-down and RIP were used to explore the interaction among PVT1, miR-325-3 and Snail1.

RESULTS

In in vivo and in vitro DN models, the expression of PVT1 was upregulated. High glucose (HG) induced cell viability, oxidative stress, fibrosis and inflammation in MCs, which were reversed in the PVT1-KD MCs. The level of miR-325-3p was also increased in in vivo and in vitro experiments. Additionally, PVT1 can directly bind to miR-325-3p. Finally, Snail1 was a direct target of miR-325-3p.

CONCLUSION

PVT1 inhibits viability, oxidative stress, fibrosis, and inflammation in DN via miR-325-3p/Snail1 axis.

背景

糖尿病肾病（DN）作为糖尿病的一种并发症，是糖尿病患者死亡的主要原因。据报道，长链非编码RNA PVT1（PVT1）可通过促进细胞外基质（ECM）积累和增加纤连蛋白1（FN1）的表达来加速DN的进展。然而，PVT1在DN中的潜在机制仍不清楚。

方法

为研究PVT1对DN的影响，给小鼠注射50 mg/kg链脲佐菌素（STZ）建立DN模型。用高糖诱导系膜细胞（MCs）作为DN的体外模型。通过qRT-PCR和蛋白质免疫印迹法评估PVT1、miR-325-3和Snail1的表达水平。采用荧光素酶报告基因检测、RNA下拉实验和RNA免疫沉淀实验来探究PVT1、miR-325-3和Snail1之间的相互作用。

结果

在体内和体外DN模型中，PVT1的表达上调。高糖（HG）诱导MCs的细胞活力、氧化应激、纤维化和炎症，而在PVT1基因敲低的MCs中这些作用得到逆转。在体内和体外实验中，miR-325-3p的水平也升高。此外，PVT1可直接与miR-325-3p结合。最后，Snail1是miR-325-3p的直接靶标。