Staff Members - Benha University
Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway
• 2019
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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publication.type
Local
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 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