Gastrin-releasing peptide promotes the migration of vascular smooth muscle cells through upregulation of matrix metalloproteinase-2 and -9
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase- 2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.
Abstract
Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase- 2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.
참고문헌 (30)
- Majumdar ID, "Biology of mammalian bombesin-like peptides and their receptors", Curr Opin Endocrinol Diabetes Obes, 18, pp.68~74 (2011)
- Gonzalez N, "Bombesin-related peptides and their receptors: Recent advances in their role in physiology and disease states", Curr Opin Endocrinol Diabetes Obes, 15, pp.58~64 (2008)
- Roesler R, "Gastrin-releasing peptide receptor signaling in the integration of stress and memory", Neurobiol Learn Mem, 112, pp.44~52 (2014)
- Rao RM, "Endothelial dependent mechanisms of leukocyte recruitment to the vascular wall", Circ Res, 101, pp.234~247 (2007)
- Sprague AH, "Inflammatory cytokines in vascular dysfunction and vascular disease", Biochem Pharmacol, 78, pp.539~552 (2009)
- Czepielewski RS, "Gastrinreleasing peptide receptor(GRPR)mediates chemotaxis in neutrophils", Proc Natl Acad Sci U S A, 109, pp.547~552 (2012)
- Kim MK, "Gastrin-releasing peptide induces monocyte adhesion to vascular endothelium by upregulating endothelial adhesion molecules", Biochem Biophys Res Commun, 485, pp.542~549 (2017)
- Owens GK, "Molecular regulation of vascular smooth muscle cell differentiation in development and disease", Physiol Rev, 84, pp.767~801 (2004)
- Abedi H, "Signalling mechanisms in the regulation of vascular cell migration", Cardiovasc Res, 30, pp.544~556 (1995)
- Newby AC, "Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates", Cardiovasc Res, 69, pp.614~624 (2006)
- Sancho V, "Bombesin receptor-mediated imaging and cytotoxicity: Review and current status", Curr Drug Deliv, 8, pp.79~134 (2011)
- Oliveira PG, "Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis", Arthritis Rheum, 63, pp.2956~2965 (2011)
- Ghosh A, "Cigarette smoke-induced MMP2 and MMP9 secretion from aortic vascular smooth cells is mediated via the Jak", Stat pathway, 2015, pp.46, 284~294
- Seki Y, "Role of the JAK", STAT pathway in rat carotid artery remodeling after vascular injury, 2000, pp.87, 12~18
- Daniel JM, "Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation", Basic Res Cardiol, 107, pp.261~272 (2012)
- Doran AC, "Role of smooth muscle cells in the initiation and early progression of atherosclerosis", Arterioscler Thromb Vasc Biol, 28, pp.812~819 (2008)
- Willis AI, "Vascular smooth muscle cell migration: Current research and clinical implications", Vasc Endovascular Surg, 38, pp.11~23 (2004)
- Dzau VJ, "Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies", Nat Med, 8, pp.1249~1256 (2002)
- Yu H, "Revisiting STAT3 signalling in cancer: New and unexpected biological functions", Nat Rev Cancer, 14, pp.736~746 (2014)
- Liao XH, "STAT3 protein regulates vascular smooth muscle cell phenotypic switch by interaction with myocardin", J Biol Chem, 290, pp.19641~19652 (2015)
- Dutzmann J, "Emerging translational approaches to target STAT3 signalling and its impact on vascular disease", Cardiovasc Res, 106, pp.365~374 (2015)
- Caird J, "Matrix metalloproteinases 2 and 9 in human atherosclerotic and nonatherosclerotic cerebral aneurysms", Eur J Neurol, 13, pp.1098~1105 (2006)
- Wagsater D, "MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr(-", -)Apob(100, Int J Mol Med, pp.2011, 28[DOI]
- Mason DP, "Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery", Circ Res, 85, pp.1179~1185 (1999)
- Belo VA, "Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension", J Vasc Res, 52, pp.221~231 (2015)
- Vincenti MP, "Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: Can MMPs be good for you?", J Cell Physiol, 213, pp.355~364 (2007)
- Sun HJ, "Salusin-beta promotes vascular smooth muscle cell migration and intimal hyperplasia after vascular injury via ROS", NFkappaB, Antioxid Redox Signal, pp.2016, 24[DOI]
- Fan Y, "NF-kappaB and STAT3 signaling pathways collaboratively link inflammation to cancer", Protein Cell, 4, pp.176~185 (2013)
- 최송희, "Effect of respiratory syncytial virus on the growth of hepatocellular carcinoma cell-lines", BMB Reports, 48(10), pp.565~570 (2015), 생화학분자생물학회
- Dan-Dan Dong, "GPR78 promotes lung cancer cell migration and metastasis by activation of Gαq-Rho GTPase pathway", BMB Reports, 49(11), pp.623~628 (2016), 생화학분자생물학회