Acute kidney injury (AKI) is the most common complication of sepsis. microRNAs (miRNAs) play important roles in the sepsis-induced AKI. This paper aimed to explore the role of miR-181a-2-3p in the sepsis-induced AKI and the underlying mechanism. Our results revealed that miR-181a-2-3p showed low expression levels in patients with sepsis and mouse models undergoing cecal ligation and puncture (CLP). The addition of miR-181a-2-3p antagonists aggravated the sepsis-induced kidney injuries and inflammatory response in CLP mouse models, as suggested by hematoxylin and eosin (H&E) staining and qRT-PCR. Besides, miR-181a-2-3p mimic alleviated the lipopolysaccharide (LPS)-induced inflammatory response, along with apoptosis of TCMK-1. Moreover, results from the GSE46955 dataset indicated that GJB2 was highly expressed in septic patients, but lowly expressed after recovery. Further, the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out, which confirmed that GJB2 was a target of miR-181a-2-3p, and over-expression of GJB2 reversed the anti-inflammatory and anti-apoptotic effects of miR-181a-2-3p mimic on the LPS-induced sepsis cell models. In conclusion, miR-181a-2-3p alleviates the inflammatory response and cell apoptosis of septic patients and animal models by up-regulating GJB2 expression, which may provide a new therapeutic strategy for sepsis.

中文翻译：

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miR-181a-2-3p通过靶向GJB2减轻脓毒症急性肾损伤肾小管上皮细胞凋亡

急性肾损伤 (AKI) 是败血症最常见的并发症。microRNA (miRNA) 在败血症诱导的 AKI 中发挥重要作用。本文旨在探讨miR-181a-2-3p在脓毒症诱导的AKI中的作用及其潜在机制。我们的结果显示 miR-181a-2-3p 在脓毒症患者和接受盲肠结扎穿刺 (CLP) 的小鼠模型中显示出低表达水平。正如苏木精和伊红 (H&E) 染色和 qRT-PCR 所表明的那样，添加 miR-181a-2-3p 拮抗剂会加剧 CLP 小鼠模型中败血症引起的肾损伤和炎症反应。此外，miR-181a-2-3p 模拟物减轻了脂多糖 (LPS) 诱导的炎症反应，以及 TCMK-1 的细胞凋亡。此外，来自 GSE46955 数据集的结果表明 GJB2 在脓毒症患者中高表达，但恢复后低表达。此外，进行了双荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定，证实 GJB2 是 miR-181a-2-3p 的靶标，并且 GJB2 的过表达逆转了抗炎和抗凋亡作用。 miR-181a-2-3p 模拟物对 LPS 诱导的败血症细胞模型的影响。总之，miR-181a-2-3p通过上调GJB2表达减轻脓毒症患者和动物模型的炎症反应和细胞凋亡，可能为脓毒症提供新的治疗策略。GJB2 的过表达逆转了 miR-181a-2-3p 模拟物对 LPS 诱导的败血症细胞模型的抗炎和抗凋亡作用。总之，miR-181a-2-3p通过上调GJB2表达减轻脓毒症患者和动物模型的炎症反应和细胞凋亡，可能为脓毒症提供新的治疗策略。GJB2 的过表达逆转了 miR-181a-2-3p 模拟物对 LPS 诱导的败血症细胞模型的抗炎和抗凋亡作用。总之，miR-181a-2-3p通过上调GJB2表达减轻脓毒症患者和动物模型的炎症反应和细胞凋亡，可能为脓毒症提供新的治疗策略。