Mechanisms of mesenchymal stem cell-derived extracellular vesicles in improvement of renal injury in rats with diabetic nephropathy by regulating mammalian target of rapamycin/p70 ribosome protein S6 kinase/coiled-coil myosin-like Bcl-2-interacting protein
Objective To explore the mechanisms of mesenchymal stem cell-derived extracellu-lar vesicles(MSC-EVs)in improvement of renal injury in rats with diabetic nephropathy(DN)by reg-ulating mammalian target of rapamycin(mTOR)/p70 ribosome protein S6 kinase(S6K1)/coiled-coil myosin-like Bcl-2-interacting protein(Beclin 1)pathway.Methods The model of SD rats with DN was established by a method of high-fat diet combined with intraperitoneal injection of streptozotocin,and they were randomly divided into model group,MSC-EVs group,and MSC-EVs+MHY1485(mTOR activator)group,with 12 rats in each group.Another 12 SD rats were normally fed for 6 weeks and then intraperitoneally injected with an equal dose of sodium citrate solution as controls.After grouping with MSC-EVs and MHY1485,blood glucose and levels of renal function indicators[blood urea nitrogen(BUN),serum creatinine(Scr),and urinary microalbumin(UmALB)]in rats were detected.HE staining was used to detect the pathological morphology of renal tissue in rats of each group;immunohistochemistry was used to detect the expression of mTOR/S6K1/Beclin 1 pathway related proteins in the renal tissues of rats in each group;the Western blot was used to de-tect the mTOR/S6K1/Beclin 1 pathway and autophagy-related protein expression in the renal tissues of rats in each group.Results Compared with the control group,the renal tissue morphology of rats in the model group were impaired,and the blood glucose,BUN,Scr,UmALB,relative positive ex-pressions of p-mTOR and p-S6K1,p-mTOR/mTOR,p-S6K1/S6K1 increased significantly(P＜0.05),while microtubule associated protein 1A/1B light chain 3(LC3)Ⅱ/LC3 Ⅰ,expression of Beclin 1 protein,and relative positive expression of Beclin 1 significantly reduced(P＜0.05);compared with the model group,the MSC-EVs group had less impairment in the renal tissue mor-phology,and the blood glucose,BUN,Scr,UmALB,relative positive expressions of p-mTOR and p-S6K1,p-mTOR/mTOR,and p-S6K1/S6K1 decreased significantly(P＜0.05),while expression of LC3 Ⅱ/LC3 Ⅰ,Beclin 1 protein,and relative positive expression of Beclin 1 increased signifi-cantly(P＜0.05);compared with the MSC-EVs group,the impairment of the renal tissue morphol-ogy was worse in the MSC-EVs+MHY1485 group,and the blood glucose,BUN,Scr,UmALB,rel-ative positive expressions of p-mTOR and p-S6K1,expression of p-mTOR/mTOR,and p-S6K1/S6K1 increased significantly(P＜0.05),while the expression of LC3Ⅱ/LC3Ⅰ,Beclin 1 protein,and rela-tive positive expression of Beclin 1 decreased significantly(P＜0.05).Conclusion MSC-EVs can enhance autophagy,reduce levels of blood glucose,Scr,BUN and urinary protein in rats with DN,alleviate renal tissue damage,and the mechanism may be achieved by inhibiting the activation of the mTOR/S6K1/Beclin 1 pathway.
mesenchymal stem cell-derived extracellular vesiclesmammalian target of rapa-mycinp70 ribosome protein S6 kinasecoiled-coil myosin-like Bcl-2-interacting proteindiabetic nephropathyrenal injury
万方数据
维普
