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Vol. 65 No. 7: Issue 7

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Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway

https://doi.org/10.14715/cmb/2019.65.7.21
Yuan Lin
Department of Endocrinology, Peking University Shenzhen Hospital, China
Fang Zhang
Department of Endocrinology, Peking University Shenzhen Hospital, China
Xiao-fen Lian
Department of Endocrinology, Peking University Shenzhen Hospital, China
Wei-qun Peng
Department of Endocrinology, Peking University Shenzhen Hospital, China
Chao-yao Yin
Department of Endocrinology, Peking University Shenzhen Hospital, China

Corresponding Author(s) : Yuan Lin

ezttz1@163.com

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7

Abstract

The aim of this study is to investigate  the effect of mesenchymal stem cell (MSC)-derived exosomes on diabetes mellitus-induced myocardial injury, and the underlying mechanism. Thirty adult male Sprague Dawley rats were randomly assigned to three groups of ten rats each: normal control group, diabetic control group and MSC exosomes group. Exosomes were isolated from MSCs through gradient ultracentrifugation. With the exception of normal control, diabetes mellitus (DM) was induced in the rats with a single intraperitoneal injection of 30 mg/kg body weight streptozotocin (STZ) in 0.1 mol/L sodium citrate buffer. Rats in MSC exosomes group were intravenously injected with MSC-derived exosomes once a week for 12 weeks. Left ventricular collagen (LVC) level was measured using acid hydrolysis method. Fatty acid transporters (FATPs) and fatty acid beta oxidase (FA-β-oxidase) were determined using enzyme-linked immunosorbent assay (ELISA). Gene and protein expressions of TGF-β and Smad2 were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting. Flow cytometric analysis and Western blotting revealed positive expression of exosomal specific marker, CD63. The level of LVC was significantly higher in diabetic control group than in normal control group, but was significantly reduced after treatment with MSC-derived exosomes (p < 0.05). The levels of FATPs and FA-β-oxidase were significantly lower in diabetic control group than in normal control group (p < 0.05). However, treatment with MSC-derived exosomes significantly increased the levels of these proteins (p < 0.05). The levels of expression of TGF-β1 and Smad2 mRNAs were significantly higher in the diabetic control group than in normal control group, but were significantly reduced after treatment with MSC-derived exosomes (p < 0.05). The expressions of TGF-β1 and Smad2 proteins were also significantly upregulated in diabetic control group, when compared with normal control group (p < 0.05). However, treatment with MSC-derived exosomes significantly down-regulated the expression of these proteins (p < 0.05). The results obtained in this study indicate that MSC-derived exosomes improve DM-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway.

Keywords

Diabetes mellitus Diabetic cardiomyopathy Mesenchymal stem cell-derived exosomes Fibrosis Expression.
Lin, Y., Zhang, F., Lian, X.- fen, Peng, W.- qun, & Yin, C.- yao. (2019). Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway. Cellular and Molecular Biology, 65(7), 123–126. https://doi.org/10.14715/cmb/2019.65.7.21
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References
  1. Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An update of mechanisms contributing to this clinical entity. Circ Res 2018; 122: 624-638.
  2. Phinney DG, Pittenger MF. Concise Review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017; 35: 851-885.
  3. Saeedi-Borujeni MJ, Esfandiary E, Taheripak G, Codoñer-Franch P, Alonso-Iglesias E, Mirzaei H. Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome. J Cell Biochem 2018; 119: 1257-1272.
  4. Tao L, Shi J, Yang X, Yang L, Hua F. The exosome: a new player in diabetic cardiomyopathy. J Cardiovasc Transl Res 2019; 12: 62-67.
  5. Lam BB, Wang JJ, Shao LB, Zhang Y, Zhou J, Meng QY, et al. Mesenchymal stem cell-derived exosomes inhibit high-glucose-induced fibroblast transdifferentiation through the TGF-β1/smad2/3 signaling pathway. Chin J Cell Biol 2017; 43: 916-925.
  6. Shao L, Zhang Y, Lan B, Wang J, Zhang Z, Zhang L, et al. MiRNA sequence indicates that mesenchymal stem cells and exosomes have similar mechanism to enhance cardiac repair. Biomed Res Int 2017; 8: 1-9.
  7. Guo S, Meng XW, Yang XS, Liu XF, Ou-Yang CH, Liu C. Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes. Acta Pharmacol Sin 2018; 39: 195-204.
  8. Li CR. Protective effects of stilbene glycoside on myocardial injury in diabetic rats. Chin Pharmacol Bull 2016; 32: 410-415.
  9. Liu T. Research progress on the relationship between mitochondrial damage and diabetic cardiomyopathy. Chin Pharmacol Bull 2018; 34: 456-458.
  10. Wang XT, Gong Y, Zhou B, Yang JJ, Cheng Y, Zhao JG, et al. Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats. Biomed Pharmacother 2018; 97: 1461-1467.
  11. Zhou G, Yang W, Li L. Effects of percutaneous coronary intervention on viable myocardium and heart function of diabetic patients with chronic total occlusion. J Comput Assist Tomogr 2017; 41: 757-761.
  12. Tsao CR, Liao MF, Wang MH, Cheng CM, Chen CH. Mesenchymal stem cell derived exosomes: a new hope for the treatment of cardiovascular disease. Acta Cardiol Sin 2014; 30: 395-400.
  13. Akyurekli C, Le Y, Richardson RB, Fergusson D, Tay J, Allan DS. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev 2015; 11: 150-160.
  14. Qi H, Liu DP, Xiao DW, Tian DC, Su YW, Jin SF. Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways. In Vitro Cell Dev Biol Anim 2019; 10: 19-33.
  15. Ma Z, Cui X, Lu L, Chen G, Yang Y, Hu Y, et al. Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis. Stem Cell Res Ther 2019; 10: 60.
  16. Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22: 845-854.
  17. Zhao Y, Sun X, Cao W, Ma J, Sun L, Qian H, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve acute myocardial ischemic injury. Stem Cells Int 2015; 6: 1-8.
  18. Yoshida K, Murata M, Yamaguchi T, Matsuzaki K. TGF-beta/Smad signaling during hepatic fibro-carcinogenesis (review). Int J Oncol 2014; 45: 1363-1371.
  19. Liu JC, Zhou L, Wang F, Cheng ZQ, Rong C. Osthole decreases collagen I/III contents and their ratio in TGF-beta1-overexpressed mouse cardiac fibroblasts through regulating the TGF-beta/Smad signaling pathway. Chin J Nat Med 2018; 16: 321-329.
  20. Shen H. The role of TGF-β/Smads signaling pathway in curcumin improving myocardial fibrosis in diabetic rats. Chin Pharmacol Bull 2018; 34: 522-527.
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