Huang Yuyu, Wang Hongwu, Wang Yanhui, Peng Xiaohui, Li Jing, Gu Wenlong, He Ting, Chen Minjun
Pharmazie. 2018 Jan 2;73(1):29-34. doi: 10.1691/ph.2018.7776.
MicroRNAs (miRs) are endogenous substances that act as important diagnostic and treatment targets in renal diseases. miR-146 plays an important role in the development of endotoxin tolerance through NF-κB pathway, but the underlying mechanism is not clearly understood. The aim of this study was to determine the molecular regulation and function of miR-146 and also the expression of miR-146 in an experimental model of renal ischemia reperfusion injury (IRI).
IRI was induced in mouse by bilateral IRI for 45 min followed by reperfusion. The male mice were randomized as: sham, I/R, I/R+miR-146, and I/R+antago-miR-146 groups. Renal function, histological damage, and cell apoptosis were evaluated at 24 h after reperfusion.
Overexpression of miR-146 protected renal function. Renal cells with upregulated miR-146 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, decreased apoptosis and active caspase-3 protein expressions. miR-146 was shown to have a role in renal IR injury. miR-146 has a protective effect on renal function and plays a significant role in apoptosis. IGSF1 acts as a target of miR-146. IGSF1 rescued the effects of miR-146 on renal IRI. miR-146 protected renal function by activation of PI3K/AKT.
These findings suggest that miR-146 might regulate apoptosis and can cause injury in I/R via targeting IGSF1 and also exert renal protection property.
微小RNA（miR）是内源性物质，在肾脏疾病中作为重要的诊断和治疗靶点。miR-146通过核因子κB（NF-κB）途径在内毒素耐受的发展中起重要作用，但其潜在机制尚不清楚。本研究的目的是确定miR-146的分子调控和功能，以及其在肾脏缺血再灌注损伤（IRI）实验模型中的表达。
通过双侧IRI 45分钟后再灌注诱导小鼠IRI。将雄性小鼠随机分为：假手术组、I/R组、I/R+miR-146组和I/R+抗miR-146组。在再灌注后24小时评估肾功能、组织学损伤和细胞凋亡。
miR-146的过表达保护了肾功能。miR-146上调的肾细胞血浆尿素氮（BUN）和肌酐水平较低，细胞凋亡减少，活化的半胱天冬酶-3蛋白表达降低。miR-146在肾脏IR损伤中发挥作用。miR-146对肾功能有保护作用，在细胞凋亡中起重要作用。免疫球蛋白超家族成员1（IGSF1）是miR-146的靶标。IGSF1挽救了miR-146对肾脏IRI的作用。miR-146通过激活磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（AKT）保护肾功能。
这些发现表明，miR-146可能通过靶向IGSF1调节细胞凋亡，并在I/R中导致损伤，同时发挥肾脏保护作用。
