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 pathway

WU Lili; LIN Jingtao; ZHANG Yuancheng; ZHONG Peimin; TANG Jinsong; WANG Haibo

doi:10.7619/jcmp.20232784

Journal of Clinical Medicine in Practice > 2024 > 28(10): 51-57. > DOI: 10.7619/jcmp.20232784

WU Lili, LIN Jingtao, ZHANG Yuancheng, ZHONG Peimin, TANG Jinsong, WANG Haibo. 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 pathway[J]. Journal of Clinical Medicine in Practice, 2024, 28(10): 51-57. DOI: 10.7619/jcmp.20232784

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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 pathway

1.
Department of Laboratory, Dongguan Dalang Hospital Guangdong Province, Dongguan, Guangdong, 523770
2.
Guangdong Medical University, Dongguan, Guangdong, 523000

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Received Date: September 02, 2023
Revised Date: October 11, 2023
Available Online: May 31, 2024

Graphical Abstract

Abstract

Abstract

Objective
To explore the mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in improvement of renal injury in rats with diabetic nephropathy (DN) by regulating 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 detect 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 expressions 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/LC3Ⅰ, 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 morphology, 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 LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 increased significantly (P < 0.05); compared with the MSC-EVs group, the impairment of the renal tissue morphology was worse in the MSC-EVs+MHY1485 group, and the blood glucose, BUN, Scr, UmALB, relative 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 relative 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.

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References (29)

References

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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 pathway

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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 pathway

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