China-Canada Joint Lab of Food Nutrition and Health (Beijing), Key Laboratory of Special Food Supervision Technology for State Market Regulation, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, 11 Fucheng Road, Haidian District, Beijing, 100048, China.
The Fourth Medical Center of PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
Eur J Trauma Emerg Surg. 2023 Apr;49(2):1035-1045. doi: 10.1007/s00068-022-02124-5. Epub 2022 Oct 13.
The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear.
In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments.
Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1).
Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI.
烧伤或脓毒症后 miRNA 谱发生改变，并参与调节炎症反应。然而，miRNAs 调节烧伤脓毒症诱导的急性肾损伤（AKI）的功能和分子机制尚不清楚。
本研究通过向烧伤大鼠注射脂多糖（LPS）或用 LPS 处理 NRK-52E 细胞，分别建立动物和细胞脓毒症模型。在进行了上述处理后，分析了细胞因子表达、炎症细胞浸润、血清肌酐（Scr）和肾损伤分子-1（KIM-1）水平。
烧伤脓毒症增加了炎症因子（TNF-α和 IL-1β）和趋化因子（MIP-1α、MIP-2 和 MCP-1）的表达。此外，烧伤脓毒症促进了巨噬细胞和中性粒细胞向肾脏浸润，并上调了肾脏和尿液中 Scr 和 KIM-1 的水平。miR-181c 的异位表达显著降低了 LPS 诱导的 TLR4 蛋白表达，抑制了 KIM-1 mRNA 水平，并随后抑制了炎症基因（TNF-α和 IL-1β）和趋化因子基因（MIP-1α、MIP-2 和 MCP-1）的激活。
我们的结果表明，miR-181c 可以抑制 TLR4 表达，减少炎症因子和趋化因子的分泌，减轻炎症细胞向肾脏浸润，并下调 KIM-1 的表达，从而最终减轻烧伤脓毒症诱导的 AKI。
