The Effect of AdipoRon on the Activity of Caspase 3, Matrix Metalloproteinases 2 and 9, and Angiogenesis in Rat Bone Marrow-Derived Mesenchymal Stem Cell

Document Type : Original Article (s)

Authors

1 MSc Student, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2 Professor, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

3 Associate Professor, Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

4 Assistant Professor, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

Background: Today, the use of mesenchymal stem cells (MSCs) is an appropriate option for the treatment of many diseases. But, poor viability, and low number of transplanted stem cells are the main obstacles in cell therapy. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. Herein, we investigated the effect of AdipoRon, adiponectin receptor agonist, on activity of caspase 3, matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), and angiogenesis in rat bone marrow-derived mesenchymal stem cells.Methods: Mesenchymal stem cells were treated with different concentrations of AdipoRon for 24 hours. The expression level of vascular endothelial growth factor (VEGF), and angiopoietin 2 and 4 (Ang-2 and Ang-4) were assessed using real-time polymerase chain reaction (real-time PCR). Gelatin zymography assay was applied to investigate the protease activity of matrix metalloproteinase 2 and 9. Measurement of caspase-3 activity was carried out via an enzymatic assay.Findings: The real-time polymerase chain reaction results indicated that the expression of vascular endothelial growth factor was higher in AdipoRon-treated mesenchymal stem cells compared to control groups when angiopoietin 2 and 4 did not show any significant change. The enzymatic activity of metalloproteinase 2 and 9 was increased in treated samples with AdipoRon compared to control group. The caspase-3 activity was attenuated in AdipoRon-pretreated cells compared to the control group.Conclusion: Based on these results, it is likely that preconditioning of mesenchymal stem cells with AdipoRon prior to transplantation can enhance the viability and migration via overexpression of vascular endothelial growth factor, activation of metalloproteinase 2 and 9 enzymes, and inhibit the activation of caspase-3.

Keywords

References

  1. Pourjafar M, Saidijam M, Mansouri K, Ghasemibasir H, Karimi DF, Najafi R. All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo. Cell Prolif 2017; 50(1).
  2. Najafi R, Sharifi AM. Deferoxamine preconditioning potentiates mesenchymal stem cell homing in vitro and in streptozotocin-diabetic rats. Expert Opin Biol Ther 2013; 13(7): 959-72.
  3. Esfahani M, Karimi F, Afshar S, Niknazar S, Sohrabi S, Najafi R. Prolyl hydroxylase inhibitors act as agents to enhance the efficiency of cell therapy. Expert Opin Biol Ther 2015; 15(12): 1739-55.
  4. Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9: 29.
  5. Srijaya TC, Ramasamy TS, Kasim NH. Advancing stem cell therapy from bench to bedside: lessons from drug therapies. J Transl Med 2014; 12: 243.
  6. Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, et al. Concise review: Mesenchymal stem cells and translational medicine: emerging issues. Stem Cells Transl Med 2012; 1(1): 51-8.
  7. Bruno S, Collino F, Tetta C, Camussi G. Dissecting paracrine effectors for mesenchymal stem cells. Adv Biochem Eng Biotechnol 2013; 129: 137-52.
  8. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med 2005; 9(2): 267-85.
  9. Leeper NJ, Hunter AL, Cooke JP. Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells. Circulation 2010; 122(5): 517-26.
  10. Yamakawa M, Liu LX, Belanger AJ, Date T, Kuriyama T, Goldberg MA, et al. Expression of angiopoietins in renal epithelial and clear cell carcinoma cells: regulation by hypoxia and participation in angiogenesis. Am J Physiol Renal Physiol 2004; 287(4): F649-F657.
  11. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 2013; 503(7477): 493-9.
  12. Guillod-Maximin E, Roy AF, Vacher CM, Aubourg A, Bailleux V, Lorsignol A, et al. Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons. J Endocrinol 2009; 200(1): 93-105.
  13. Malih S, Saidijam M, Mansouri K, Pourjafar M, Tafakh MS, Talebzadeh F, et al. Promigratory and proangiogenic effects of AdipoRon on bone marrow-derived mesenchymal stem cells: An in vitro study. Biotechnol Lett 2017; 39(1): 39-44.
  14. Wislet-Gendebien S, Laudet E, Neirinckx V, Rogister B. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders? J Biomed Biotechnol 2012; 2012: 601560.
  15. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004; 36(4): 568-84.
  16. Dadson K, Chasiotis H, Wannaiampikul S, Tungtrongchitr R, Xu A, Sweeney G. Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts. J Cell Biochem 2014; 115(4): 785-93.
  17. Adya R, Tan BK, Chen J, Randeva HS. Protective actions of globular and full-length adiponectin on human endothelial cells: Novel insights into adiponectin-induced angiogenesis. J Vasc Res 2012; 49(6): 534-43.
  18. Tsai JR, Liu PL, Chen YH, Chou SH, Cheng YJ, Hwang JJ, et al. Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-kappab/MMPs Signaling Pathway. PLoS One 2015; 10(12): e0144462.
  19. Lee HP, Lin CY, Shih JS, Fong YC, Wang SW, Li TM, et al. Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-alpha pathway. Oncotarget 2015; 6(34): 36746-61.
  20. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 2004; 279(2): 1304-9.
  21. Jones N, Iljin K, Dumont DJ, Alitalo K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol 2001; 2(4): 257-67.
  22. Marina Garcia J, Goldenthal MJ, Moe GW. Aging and the heart: A post-genomic view. New York, NY: Springer; 2007.
  23. Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 2009; 4(3): 206-16.
  24. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 2005; 11(10): 1096-103.
  25. Zhang Y, Zhao J, Li R, Lau WB, Yuan YX, Liang B, et al. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings. Am J Physiol Endocrinol Metab 2015; 309(3): E275-E282.
Journal of Isfahan Medical School
Volume 36, Issue 465 - Serial Number 465
January and February 2018
Pages 1-7

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History

  • Receive Date: 30 October 2017
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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