Dina Sabry

Citation:

Ebrahim, N., I. A. Ahmed, N. I. Hussien, A. A. Dessouky, A. S. Farid, A. M. Elshazly, O. Mostafa, W. B. E. Gazzar, S. M. Sorour, Y. Seleem, et al., "Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway.", Cells, vol. 7, issue 12, 2018 Nov 22.

Abstract:

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes.

RESULTS: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA.

CONCLUSION: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.