Staff Members - Benha University
Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway
• 2018
Publication Information
Authors
Nesrine Ebrahim 1,2, Inas A. Ahmed 3,4, Noha I. Hussien 5, Arigue A. Dessouky 6,Ayman Samir Farid 7,* , Amal M. Elshazly 8, Ola Mostafa 1, Walaa Bayoumie El Gazzar 3,Safwa M. Sorour 9, Yasmin Seleem 9, Ahmed M. Hussein 10 and Dina Sabry 11,12
Keywords
diabetic nephropathy; exosomes; autophagy; mTOR
Journal
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Pages
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publication.type
International
Paper Link
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Supplementary Materials
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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.
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.