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Cells 2018, 7(12), 226; https://doi.org/10.3390/cells7120226

Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway

1
Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
2
Stem Cell Unit, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
3
Department of Medical Biochemistry, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
4
Molecular Biology and Biotechnology Unit, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
5
Department of Physiology, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
6
Department of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
7
Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, QG, Egypt
8
Department of Anatomy, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
9
Department of Clinical Pharmacology, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
10
Department of Internal Medicine, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt
11
Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
12
Molecular Biology and Stem Cell Unit, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
*
Author to whom correspondence should be addressed.
Received: 11 October 2018 / Revised: 19 November 2018 / Accepted: 21 November 2018 / Published: 22 November 2018
(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)
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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. View Full-Text
Keywords: diabetic nephropathy; exosomes; autophagy; mTOR diabetic nephropathy; exosomes; autophagy; mTOR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ebrahim, N.; Ahmed, I.A.; Hussien, N.I.; Dessouky, A.A.; Farid, A.S.; Elshazly, A.M.; Mostafa, O.; Gazzar, W.B.E.; Sorour, S.M.; Seleem, Y.; Hussein, A.M.; Sabry, D. Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway. Cells 2018, 7, 226.

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