Introduction

The present study aimed to investigate whether miR-129-5p can regulate high-mobility group box protein 1 (HMGB1)-modulated TLRs/NF-kappaB inflammatory pathway that contributed to lipopolysaccharide (LPS)-induced podocyte apoptosis and acute kidney injury (AKI).

Material and methods

In vitro and in vivo models of sepsis were simulated using LPS-administrated podocytes and mice, respectively. The effects of LPS, mR-129-5p mimics and short hairpin RNA of HMGB1 (sh-HMGB1) on podocyte apoptosis were monitored using TUNEL staining. Protein expression was measured using western blotting. Survival outcomes were analyzed in septic mice with agomir-mR-129-5p administration.

Results

We observed that stimulation of podocytes with LPS significantly inhibits the expression of miR-129-5p, and overexpression of miR-129-5p protects against LPS-induced podocyte damage, over-activation of inflammatory response and apoptosis. In a mouse model, agomir-miR-129-5p administration significantly improves the survival outcomes in septic mice and LPS-induced AKI. Mechanically, LPS-induced the elevation of HMGB1, TLR2, TLR4 and nuclear NF-κB protein expression in vitro and in vivo are restrained by the overexpression of miR-129-5p.

Conclusions

Overexpression of miR-129-5p protects against LPS-induced podocyte apoptosis, inflammation and AKI in vivo and in vitro models of sepsis. The underlying molecular mechanism is mediated via attenuating HMGB1/TLRs/NF-κB signaling axis modulated inflammatory response.

中文翻译：

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miR-129-5p通过靶向HMGB1 / TLRs /NF-κB途径减轻LPS诱导的急性肾损伤

介绍

本研究旨在调查miR-129-5p是否可以调节高迁移率族蛋白1（HMGB1）调节的TLRs / NF-kappaB炎性途径，从而导致脂多糖（LPS）诱导足细胞凋亡和急性肾损伤（AKI） ）。

材料与方法

分别使用LPS给予的足细胞和小鼠模拟了脓毒症的体外和体内模型。使用TUNEL染色监测LPS，mR-129-5p模拟物和HMGB1的短发夹RNA（sh-HMGB1）对足细胞凋亡的影响。使用蛋白质印迹法测量蛋白质表达。在使用agomir-mR-129-5p的脓毒症小鼠中分析了生存结果。

结果

我们观察到，用LPS刺激足细胞可显着抑制miR-129-5p的表达，而miR-129-5p的过表达可防止LPS诱导的足细胞损伤，炎症反应过度激活和细胞凋亡。在小鼠模型中，agomir-miR-129-5p给药可显着改善败血性小鼠和LPS诱导的AKI的存活结果。从机械上讲，miR-129-5p的过表达抑制了LPS诱导的HMGB1，TLR2，TLR4和核NF-κB蛋白表达的升高。

结论

在脓毒症的体内和体外模型中，miR-129-5p的过度表达可防止LPS诱导的足细胞凋亡，炎症和AKI。潜在的分子机制是通过减弱HMGB1 / TLRs /NF-κB信号轴调节的炎症反应介导的。