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