Open AccessExosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury
Author(s) -
Jinshi Zhang,
Wenfang He,
Danna Zheng,
Qiang He,
Ming Tan,
Juan Jin
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12435
Subject(s) - microvesicles , mesenchymal stem cell , microrna , cell cycle , cancer research , flow cytometry , cisplatin , apoptosis , biology , acute kidney injury , exosome , oncogene , cell , microbiology and biotechnology , immunology , medicine , chemotherapy , gene , biochemistry , genetics
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.