Journal Article

Exosome secreted from adipose-derived stem cells attenuates diabetic nephropathy by promoting autophagy flux and inhibiting apoptosis in podocyte

Gong, Jianguang, Huang, He, Zhao, Li, Jin, Juan, He, Qiang, Shi, Yifen, Li, Yiwen

2019

Overview

Background It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice. Currently, exosome from urine-derived stem cells (USCs) can protect type 1 diabetes-mediated kidney injury and attenuate podocyte damage in diabetic nephropathy (DN). Exosome derived from USCs has evolved into the strategy for DN treatment, but the role of ADSCs-derived exosome (ADSCs-Exo) in DN remains unclear. The present study is aimed to investigate the therapeutic action and molecular mechanism of ADSCs-derived exosome on DN. Methods ADSCs and exosome were authenticated by immunofluorescence and flow cytometry. Morphology and the number of exosome were evaluated by electron microscope and Nanosight Tracking Analysis (NTA), respectively. Cell apoptosis was assessed using flow cytometry. Podocyte autophagy and signaling transduction were measured by immunofluorescence and immunoblotting. Dual Luciferase Reporter assay was employed to detect the regulatory relationship between miR-486 and Smad1. Results ADSCs-Exo attenuated spontaneous diabetes by reducing levels of urine protein, serum creatinine (Scr), blood urea nitrogen (BUN), and podocyte apoptosis in mice. In in vitro experiment, ADSCs-Exo also reversed high glucose-induced decrease of cell viability and the increase of cell apoptosis in MPC5 cells. In terms of mechanism, ADSCs-Exo could enhance autophagy flux and reduce podocyte injury by inhibiting the activation of mTOR signaling in MPC5 and spontaneous diabetic mice. Eventually, we found that miR-486 was the key factors in ADSCs and in the process of ADSCs-Exo-mediated improvement of DN symptom in vivo and in vitro. miR-486 reduced Smad1 expression by target regulating Smad1 whose reduction could inhibit mTOR activation, leading to the increase of autophagy and the reduction of podocyte apoptosis. Conclusions In conclusion, we illustrated that ADSCs-Exo vividly ameliorated DN symptom by enhancing the expression of miR-486 which led to the inhibition of Smad1/mTOR signaling pathway in podocyte. Possibly, ADSCs-Exo was used as a main therapeutic strategy for DN in future.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adipose Tissue - metabolism / Adipose Tissue - pathology / Adipose-derived stem cells / Animal experimentation / Animals / Apoptosis / Autophagic Cell Death / Autophagy / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Cancer / Care and treatment / Cell adhesion & migration / Cell autophagy / Cell Biology / Cell Line / Cell viability / Cellular signal transduction / Creatinine / Development and progression / Diabetes / Diabetes mellitus / Diabetes mellitus (insulin dependent) / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Experimental - metabolism / Diabetes Mellitus, Experimental - pathology / Diabetes Mellitus, Experimental - therapy / Diabetic nephropathies / Diabetic Nephropathies - metabolism / Diabetic Nephropathies - pathology / Diabetic Nephropathies - therapy / Diabetic nephropathy / Disease / Electron microscopy / Exosome / Fibrosis / Flow cytometry / Fluorescent antibody technique / Gene expression / Genetic aspects / Glucose / Homeostasis / Immunoblotting / Immunofluorescence / Kidney diseases / Kidney transplantation / Kidneys / Kinases / Laboratory animals / Life Sciences / Luciferase / Male / Mesenchymal Stem Cell Transplantation / Mesenchymal Stem Cells - metabolism / Mesenchymal Stem Cells - pathology / Mice / MicroRNA / MicroRNAs / miR-486 / Nephropathy / Phagocytosis / Podocyte damage / Podocytes - metabolism / Podocytes - pathology / Proteins / Regenerative Medicine/Tissue Engineering / Signal transduction / Smad1/mTOR signaling / Stem cell transplantation / Stem Cells / Surgery / TOR protein / Type 1 diabetes / Type 2 diabetes / Urea / Urine / Wound healing