Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy <i>via</i> the tumour necrosis factor receptor-associated factor 6/Akt axis
Xia Cai, Fang Zou, Rui Xuan, Xiaoyang Lai
Abstract
Diabetic nephropathy (DN) seriously threatens the health of patients with diabetes. Moreover, it has been reported that mesenchymal stem cell (MSC)-derived exosomal miRNAs can modulate the progression of multiple diseases, including DN. It has been suggested that miR-125b is involved in DN. However, the biological functions of exosomal miRNAs, especially miR-125b, in DN are still unclear. To establish a DN model in vitro, we used a model of human embryonic kidney epithelial cells (HKCs) injury induced by high glucose (HG). Then, miR-125b was delivered to the model cells in vitro via MSC-derived exosomes (MSC-Exos), and the effect of exosomal miR-125b on HKCs apoptosis was evaluated by flow cytometry. qRT-PCR or western blotting was performed to measure miR-125b or tumour necrosis factor receptor-associated factor 6 (TRAF6) expression in HKC. The effect of MSC-Exos on HKCs apoptosis after miR-125b knockdown was determined by flow cytometry. Moreover, dual-luciferase reporter assays were used to determine the targeting relationship between miR-125b and TRAF6 in HKCs. Our data revealed that MSC-Exos increased HG-induced autophagy in HKCs and reversed HKCs apoptosis. Moreover, our study found that miR-125b was enriched in MSC-Exos and directly targeted TRAF6 in HKCs. In addition, exosomally transferred miR-125b inhibited the apoptosis of HG-treated HKCs by mediating Akt signalling. In summary, MSC-derived exosomal miR-125b induced autophagy and inhibited apoptosis in HG-treated HKCs via the downregulation of TRAF6. Therefore, our study provided a new idea for DN treatment.