Abstract
BackgroundIt 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.MethodsADSCs 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.ResultsADSCs-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.ConclusionsIn 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.
Highlights
It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice
Adipose-derived stem cells (ADSCs) possesses strong differentiation capability In order to obtain ADSCs-derived exosome, ADSCs were isolated from subcutaneous adipose tissue in groin of C57BL/KsJ db/m mice
alkaline phosphatase (ALP) activity detection and Alizarin Red Staining results were the indicators of osteogenic capability of ADSCs which showed that osteogenic medium significantly induced the level of ALP and the number of Alizarin Red staining positive cells in ADSCs (Additional file 1: Figure S2D–E)
Summary
It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice. Exosome from urine-derived stem cells (USCs) can protect type 1 diabetes-mediated kidney injury and attenuate podocyte damage in diabetic nephropathy (DN). The pathogenesis of podocyte injury-mediated DN remains vague and therapeutic strategies for DN are lacking. Podocyte autophagy is mainly responsible for protein and organelle degradation following by regulating cell homeostasis, whose dysfunction is regarded as an essential induction factor of podocyte injury [6, 7]. MTOR signaling activation is closely linked to the accelerated podocyte injury in DN patients which potentially suggests an involvement of mTOR signaling-mediated autophagy dysfunction in DN disease [10, 11]. Autophagy flux might be a therapeutic target in podocyte damage-derived DN disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
