Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Nesrine Ebrahim
,
Inas A. Ahmed
,
Noha I. Hussien
,
Arigue A. Dessouky
,
Ayman Samir Farid
* ORCID logo ,
Amal M. Elshazly
,
Ola Mostafa
,
Walaa Bayoumie El Gazzar
,
Safwa M. Sorour
,
Yasmin Seleem
,
Ahmed M. Hussein
,
Dina Sabry
Version 1 : Received: 8 September 2018 / Approved: 10 September 2018 / Online: 10 September 2018 (06:26:55 CEST)

How to cite: Ebrahim, N.; Ahmed, I.A.; Hussien, N.I.; Dessouky, A.A.; Farid, A.S.; Elshazly, A.M.; Mostafa, O.; El Gazzar, W.B.; Sorour, S.M.; Seleem, Y.; Hussein, A.M.; Sabry, D. Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through mTOR Signaling Pathway. Preprints 2018, 2018090153. https://doi.org/10.20944/preprints201809.0153.v1 Ebrahim, N.; Ahmed, I.A.; Hussien, N.I.; Dessouky, A.A.; Farid, A.S.; Elshazly, A.M.; Mostafa, O.; El Gazzar, W.B.; Sorour, S.M.; Seleem, Y.; Hussein, A.M.; Sabry, D. Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through mTOR Signaling Pathway. Preprints 2018, 2018090153. https://doi.org/10.20944/preprints201809.0153.v1

Abstract

Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its 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) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Keywords

diabetic nephropathy; exosomes; autophagy; mTOR

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: 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.

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