Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR‑1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro, HK‑2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit‑8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription‑quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL‑1β and TNF‑α in the cell supernatants. The results revealed that miR‑1184 expression was downregulated in AKI. Exosomes derived from miR‑1184 agomir‑treated mesenchymal stem cells (MSCs) significantly reversed cisplatin‑induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR‑1184, and exosomes expressing miR‑1184 notably inhibited cisplatin‑induced inflammatory responses in HK‑2 cells via the mediation of IL‑1β and TNF‑α. Furthermore, exosomes derived from miR‑1184 agomir‑treated MSCs significantly induced G1 phase arrest in HK‑2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal‑miR‑1184 derived from MSCs alleviates cisplatin‑associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.

中文翻译：

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来自间充质干细胞的外泌体-miR-1184 可减轻顺铂相关的急性肾损伤。

急性肾损伤 (AKI) 对人类健康构成严重威胁。已知 MicroRNAs (miRNAs/miRs) 参与 AKI 的进展；然而，miR-1184 在 AKI 中的功能仍不清楚。因此，本研究的目的是检查这种 miRNA 在肾损伤中的作用。为了在体外模拟 AKI, HK-2 细胞用顺铂处理。进行生物信息学分析以探索 AKI 中差异表达的 miRNA。进行细胞计数试剂盒-8 测定和流式细胞术以分别检查细胞活力和细胞凋亡。通过逆转录定量PCR检测mRNA表达水平，并通过蛋白质印迹分析研究蛋白质水平。进行ELISA以检查细胞上清液中IL-1β和TNF-α的水平。结果显示miR-1184表达在AKI中下调。来自 miR-1184 agomir 处理的间充质干细胞 (MSCs) 的外泌体通过抑制细胞凋亡显着逆转顺铂诱导的细胞生长抑制。此外，叉头盒 O4 (FOXO4) 被发现是 miR-1184 的直接目标，表达 miR-1184 的外泌体通过 IL-1β 和 TNF-α 的介导显着抑制顺铂诱导的 HK-2 细胞炎症反应。此外，源自 miR-1184 agomir 处理的 MSCs 的外泌体通过 FOXO4、p27 Kip1 和 CDK2 的调节显着诱导 HK-2 细胞的 G1 期停滞。总之，本研究表明源自 MSCs 的外泌体-miR-1184 可缓解顺铂相关的 AKI。因此，本文提出的研究结果可能为探索治疗 AKI 的新策略提供新的思路。本研究表明，源自 MSCs 的外泌体-miR-1184 可缓解顺铂相关的 AKI。因此，本文提出的研究结果可能为探索治疗 AKI 的新策略提供新的思路。本研究表明，源自 MSCs 的外泌体-miR-1184 可缓解顺铂相关的 AKI。因此，本文提出的研究结果可能为探索治疗 AKI 的新策略提供新的思路。