Title of article :
Autophagy-induced mesenchymal stem cell-derived extracellular vesicles ameliorated renal fibrosis in an in vitro model
Author/Authors :
Ahrabi ، Behnaz Department of Biology and Anatomical Sciences - school of medicine, Laser Applications in Medical Sciences Research Center - Shahid Beheshti University of Medical Sciences , Abbaszadeh ، Hojjat Allah Department of Biology and Anatomical Sciences - Hearing Disorders Research Center, Loghman Hakim Hospital,school of medicine,Laser Applications in Medical Sciences Research Center - Shahid Beheshti University of Medical Sciences , Piryaei ، Abbas , Shekari ، Faezeh Department of Stem Cells and Developmental Biology - Cell Science Research Center - Royan Institute for Stem Cell Biology and Technology , Ahmady Roozbahany ، Navid Private Practice, Bradford , Rouhollahi ، Mahya Department of Stem Cells and Developmental Biology - Cell Science Research Center - Royan Institute for Stem Cell Biology and Technology , Azam Sayahpour ، Forough Department of Stem Cells and Developmental Biology - Cell Science Research Center - Royan Institute for Stem Cell Biology and Technology , Ahrabi ، Mahnaz Department of Endodontics - Dental Faculty - Tabriz University of Medical Sciences , Azimi ، Hadi Department of English Language Teaching - School of Medicine - Shahid Beheshti University of Medical Sciences , Moghadasali ، Reza Department of Stem Cells and Developmental Biology - Cell Science Research Center - Royan Institute for Stem Cell Biology and Technology
From page :
359
To page :
372
Abstract :
Introduction: Chronic and progressive damage to the kidney by inflammatory processes, may lead to an increase in the extracellular matrix production, a condition known as renal fibrosis. The current study aims to evaluate if the extracellular vesicles (EVs) derived from autophagic adipose-derived mesenchymal stem cells (ADMSCs) can reduce the inflammation and extracellular matrix accumulation in damaged kidney tissue. Methods: Autophagy was induced in ADMSCs using 2µM concentration curcumin and was confirmed by evaluating LC3B, ATG7, and Beclin1 using real-time polymerase chain reaction (PCR) and Western blot. An in vitro renal fibrotic model was established in HEK-293 cells exposed to H2O2 (0.8mM) for 24 and 72 hours. The fibrotic model was confirmed through evaluation of collagen I, transforming growth factor-beta 1 (TGF-β1), E-cadherin, and vimentin genes expression using real-time PCR, collagen I protein by ELISA. After induction of fibrosis for 24 and 72 hours, the HEK cells were treated with NEVs (non-autophagy EVs) (50µM) or AEVs (autophagy EVs) (50µM) at 48, 96, and 124 hours, and then the samples were collected at 72 and 148 hours. Expression of collagen I, TGF-β1, E-cadherin, and vimentin Genes was evaluated via RT-PCR, and protein levels of IL1, TNF-α, IL4, IL10 using ELISA. Results: Induction of autophagy using curcumin (2µM) for 24 hours significantly increased LC3B, Beclin1, and ATG7 in the ADMSCs. Upregulation in anti-fibrotic (E-cadherin) and anti-inflammatory (IL4, IL10) gene expression was significantly different in the fibrotic model treated by AEVs compared to NEVs. Also, the downregulation of fibrotic (TGF-β1, vimentin, collagen I) and pro-inflammatory (IL1, TNFα) gene expression was significantly different in AEVs compared with those treated by NEVs. Conclusion: Our findings suggest that AEVs can be considered as a therapeutic modality for renal fibrosis in the future.
Keywords :
Adipose , derived mesenchymal stem cells , Autophagy , Fibrosis , Extracellular vesicle
Journal title :
Bioimpacts
Journal title :
Bioimpacts
Record number :
2750882
Link To Document :
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