Zhao Ningmin, Luo Qing, Lin Ruijuan, Li Qiaoyan, Ma Peizhi
Department of Pharmacy, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.
Clin Exp Nephrol. 2021 Nov;25(11):1182-1192. doi: 10.1007/s10157-021-02102-y. Epub 2021 Jun 18.
Tubular injury plays a crucial role in the pathogenesis of diabetic nephropathy (DN). It is well known that many microRNAs (miRNAs) exert crucial effects on tubular injury. This study intends to explore the effect of miR-142-3p on the apoptosis and oxidative stress of high glucose (HG)-treated renal tubular epithelial cells (HK-2) and its underlying mechanism.
HK-2 cells were exposed to HG to mimic cell injury. MTT assays and flow cytometry analyses were conducted to measure cell viability and cell apoptosis, respectively. RT-qPCR and western blot analyses were carried out to detect RNA and protein levels, respectively. The levels of oxidative stress markers were evaluated by ELISA. The binding between miR-142-3p and biorientation of chromosomes in cell division 1 (BOD1) was validated by a luciferase reporter assay.
MiR-142-3p is low-expressed in HG-stimulated HK-2 cells. Functionally, miR-142-3p overexpression attenuates the apoptosis and oxidative stress of HG-stimulated HK-2 cells. Mechanistically, BOD1 was confirmed to be targeted by miR-142-3p in HK-2 cells. Moreover, BOD1 overexpression reversed the suppressive effect of miR-142-3p overexpression on the apoptosis and oxidative stress of HK-2 cells treated with HG.
MiR-142-3p ameliorates HG-induced renal tubular epithelial cell injury by targeting BOD1. The finding might provide novel insight into the role of miR-142-3p/BOD1 axis in DN treatment.
肾小管损伤在糖尿病肾病（DN）的发病机制中起关键作用。众所周知，许多微小RNA（miRNA）对肾小管损伤发挥关键作用。本研究旨在探讨miR-142-3p对高糖（HG）处理的肾小管上皮细胞（HK-2）凋亡和氧化应激的影响及其潜在机制。
将HK-2细胞暴露于HG以模拟细胞损伤。分别进行MTT试验和流式细胞术分析以测量细胞活力和细胞凋亡。分别进行RT-qPCR和蛋白质印迹分析以检测RNA和蛋白质水平。通过酶联免疫吸附测定（ELISA）评估氧化应激标志物的水平。通过荧光素酶报告基因测定验证miR-142-3p与细胞分裂1中染色体双定向（BOD1）之间的结合。
miR-142-3p在HG刺激的HK-2细胞中低表达。在功能上，miR-142-3p过表达减轻了HG刺激的HK-2细胞的凋亡和氧化应激。从机制上讲，在HK-2细胞中证实BOD1是miR-142-3p的靶标。此外，BOD1过表达逆转了miR-142-3p过表达对HG处理的HK-2细胞凋亡和氧化应激的抑制作用。
miR-142-3p通过靶向BOD1改善HG诱导的肾小管上皮细胞损伤。这一发现可能为miR-142-3p/BOD1轴在DN治疗中的作用提供新的见解。
