Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Abstract

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 G 1 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.

Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM

“…miRNAs are a class of endogenous noncoding single-stranded RNA molecules with a length of approximately 22 nucleotides that are widely found in eukaryotes, and they perform important roles in organism development, cell differentiation and homeostasis [ 31 – 33 ]. Recent studies have demonstrated that MSC-Exos exert protective effects through miRNAs in multiple kidney diseases [ 34 – 36 ]. Therefore, we speculated that certain miRNAs contained in exosomes may be involved in the alleviation of renal fibrosis.…”

The role of small extracellular vesicle non-coding RNAs in kidney diseases

“…As an example of this, Cao et al (2021) confirmed that sEV-miR-125b-5p from mesenchymal stem cells (MSCs) could stimulate tubular repair by suppressing p53 in AKI. Similarly, our laboratory discovered that sEV-miR-1184 from MSCs can mitigate cisplatin-associated AKI ( Zhang et al, 2021 ). Additionally, sEVs from three-dimensional (3D) cultures of human placental MSCs (hPMSCs) have been reported to be effective for the treatment of AKI ( Zhang et al, 2022 ).…”

Mesenchymal Stem Cells in the Treatment of Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD) and the AKI-to-CKD Transition

“…[60] Additionally, recent reports have demonstrated that hypoxic mesenchymal stem cells ameliorate acute kidney ischemiareperfusion injury via enhancing renal tubular autophagy, [65] and exosomal-miR-1184 derived from MSCs alleviates cisplatin-associated AKI in in vitro model using renal HK2 cells. [66]…”