Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p

Abstract

Diabetic kidney disease (DKD) is well-acknowledged as one of the most common complications in diabetes mellitus. Recent studies have demonstrated the promising role of mesenchymal stem cell-derived exosomes (MSC-exos) as a cell-free treatment strategy for DKD. The present study sought to investigate the therapeutic potential and the underlying mechanisms of MSC-exos in DKD. The authentication of MSC-exos was validated by western blot, transmission electron microscope (TEM), and nanosight tracking analysis (NTA). Apoptosis was detected by western blot, TUNEL staining, and flow cytometry. Epithelialto-mesenchymal transition (EMT) was evaluated by western blot and immunofluorescence. The relationship between miR-424-5p and Yes-associated protein 1 (YAP1) was revealed by dual luciferase reporter assay. We observed that MSCexos could attenuate DKD by decreasing cell apoptosis and inhibiting epithelialto-mesenchymal transition (EMT) in diabetic kidneys in db/db mice. Besides, we documented that MSC-exos could reverse high glucose-induced apoptosis and EMT in HK2 cells. Interestingly, miR-424-5p derived from MSC-exos could inhibit YAP1 activation in HK2 cells, resulting in alleviation of high glucose-induced cell apoptosis and EMT. Our study provides novel insights into MSC-exos-mediated protective effect in DKD. MSC-exos could inhibit high glucose-induced apoptosis and EMT through miR-424-5p targeting of YAP1.

Human placenta‐derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/ regulatory T‐cell balance through the programmed death 1 / programmed death‐ligand 1 pathway

“…30 Similarly, Cui et al found that exosomes derived from MSCs attenuate DKD by inhibiting cell apoptosis and epithelialto-mesenchymal transition via miR-424-5p. 31 These results indicate that MSC-derived exosomes may be a promising therapeutic cell-free strategy for DKD. Additionally, the latest study showed that MSCs protect kidney injury in diabetic rats through an autophagy-mediated antisenescent mechanism.…”

“…Wang et al reported that MSC‐derived exosomes transferring miR‐22‐3p ameliorate DKD through the NLRP3 signalling pathway 30 . Similarly, Cui et al found that exosomes derived from MSCs attenuate DKD by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p 31 . These results indicate that MSC‐derived exosomes may be a promising therapeutic cell‐free strategy for DKD.…”

Mesenchymal Stem Cell Therapy in Kidney Diseases: Potential and Challenges

“…Alasmari et al 77 illustrated that exosomes derived from BMMSCs impeded the progression of CKD by interfering with fibrosis and apoptosis. Moreover, MSCs-Exo exhibited anti-apoptotic effect on KD progression by transferring miRNAs (eg, miR-199a-3p 44 and miR-424-5p 81 ). What’s more, exosomes released from MSCs preconditioned with melatonin blocked apoptosis by decreasing the levels of caspase-3 67 , which had a protective effect against CKD.…”

Mesenchymal stem cell‐derived extracellular vesicles in treatment against renal fibrosis

“…55 The study revealed that miR-133b reduced TGFβ1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO. 57 In addition, MSC-EVs also suppress EMT via several other pathways. Cui et al observed that MSC-EVs decreased renal cell apoptosis and inhibited EMT in diabetic kidneys in diabetes/diabetes mice.…”