Downregulation of miRNA-1-3p modulates cyclic stretch-mediated proliferation of vascular smooth muscle cells through regulation of ETS-1
Keywords:miRNA-1-3p, cell proliferation, phenotypic switch, cyclic stretch, vascular smooth muscle cells
- Mechanical stretch modulates the proliferation of vascular smooth muscle cells (VSMCs) which plays an important role in hypertension pathogenesis.
- The role of miRNA-1-3p which is downregulated in the aorta of the spontaneous hypertension rat (SHR), on the proliferation of VSMCs induced by mechanical cyclic stretch was investigated.
- MiRNA-1-3p regulates VSMC functioning through regulation of ETS-1 during hypertension-induced vascular remodeling. Dual luciferase reporter assays revealed that V-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1) is the direct target of miRNA-1-3p.
- MiRNA-1-3p may be a viable therapeutic target for hypertension.
Abstract: Mechanical stretch modulates the proliferation of vascular smooth muscle cells (VSMCs) and plays an important role in the pathogenesis of hypertension, but the underlying mechanisms are unclear. We investigated the role of microRNA-1-3p (miRNA-1-3p) on the proliferation of VSMCs induced by mechanical cyclic stretch. Our data show that miRNA-1-3p is downregulated in the aorta of the spontaneous hypertension rat (SHR). Pathological mechanical stretch at 15% suppressed the expression of miRNA-1-3p, calponin and SM22, but enhanced the proliferation of VSMCs as well as the expression of the V-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1), collagen type I alpha (Col-1a), collagen type III alpha (Col-3a) and elastin. Overexpression of miRNA-1-3p inhibited cell proliferation and induced the expression of calponin and SM22, but decreased the expression of ETS-1, Col-1a, Col-3a and elastin. Mechanical stretch at 15% combined with losartan treatment increased the expression of miRNA-1-3p, calponin and SM22, and decreased the expression of ETS-1, Col-1a and Col-3a. Dual luciferase reporter assays revealed ETS-1 as a direct target of miRNA-1-3p. These findings suggest that miRNA-1-3p regulates VSMC function through ETS-1 regulation during hypertension-induced vascular remodeling. MiRNA-1-3p may be a viable therapeutic target for hypertension.
Yamashiro Y, Yanagisawa H. The molecular mechanism of mechanotransduction in vascular homeostasis and disease. Clin Sci (Lond). 2020;134(17):2399-418.
Rodríguez AI, Csányi G, Ranayhossaini DJ, Feck DM, Blose KJ, Assatourian L, Vorp DA, Pagano PJ. MEF2B-Nox1 signaling is critical for stretch-induced phenotypic modulation of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2015;35(2):430-8.
Wang WB, Li HP, Yan J, Zhuang F, Bao M, Liu JT, Qi YX, Han Y. CTGF regulates cyclic stretch-induced vascular smooth muscle cell. proliferation via microRNA-19b-3p. Exp Cell Res. 2019;376(1):77-85.
Orang AV, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to miRNA-Specific upregulation. Int J Genomics. 2014;2014:970607.
Shi L, Tian C, Sun L, Cao F, Meng Z. The incRNA TUG1/miR-145-5P/FGF10 regulates proliferation and migration in vsmcs of hypertension. Biochem Biophys Res Commun. 2018;501(3):688-95.
Gareri C, De Rosa S, Indolfi C. Micro RNAs for Restenosis and Thrombosis After Vascular injury. Circ Res. 2016;118(7):1170-84.
Zheng XT, Wu ZH, Xu K, Qiu YH, Su X, Zhang Z, Zhou MT. Interfering histone deacetylase 4 inhibits the proliferation of vascular smooth muscle cells via regulating MEG3/miR-125a-5p/IRF1. Cell Adh Migr. 2019;13(1):41-9.
Farina FM, Hall IF, Serio S, Zani S, Climent M, Salvarani N, Carullo P, Civilini E, Condorelli G, Elia L, Quintavalle M. miR-128-3p Is a Novel Regulator of Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Diseases. Circ Res. 2020;126(12):e120-35.
Hu B, Song JT, Qu HY, Bi CL, Huang XZ, Liu XX, Zhang M. Mechanical stretch suppresses microRNA-145 expression by activating extracellular signal-regulated kinase 1/2 and upregulating angiotensin-converting enzyme to alter vascular smooth muscle cell phenotype. PLoS One. 2014;9(5):e96338.
Turczynska K M, Bhattachariya A, Säll J, Göransson O, Swärd K, Hellstrand P, Albinsson S. Stretch-sensitive down regulation of the miR - 144/451 cluster in vascular smooth muscle and its role in AMP-activated protein kinase signaling. PLoS One. 2013;8(5):e65135.
Kura B, Kalocayova B, Devaux Y, Bartekova M. Potential Clinical Implications of miR-1 and miR-21 in Heart Disease and Cardioprotection. Int J Mol Sci. 2020;21(3):700.
Han C, Shen JK, Hornicek FJ, Kan QC, Duan ZF. Regulation of microRNA-1 (miR-1) expression in human cancer. Biochim Biophys Acta Gene Regul Mech. 2017;1860(2):227-32.
Zhang H, Zhang ZY, Gao LL, Qiao ZD, Yu MH, Yu B, Yang T. miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9. Onco Targets Ther. 2019;12:2149–57.
Chen YC, Wu CC, Tu YT, Chen YR, Ming-Cheng Lee MC, Tsai KW. Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion. Anticancer Res. 2020;40(11):6247-56.
Moreno EC, Pascual A, Prieto-Cuadra D, Laza VF, Molina-Cerrillo J, Ramos-Muñoz ME, Rodríguez-Serrano EM, Soto JL, Carrato A, García-Bermejo ML, Guillén-Ponce C. Novel molecular characterization of colorectal primary tumors based on miRNAs. Cancers (Basel). 2019;11(3):346.
Wang ZS, Wang JL, ChenZH, Wang K, Shi LS. inhibits the proliferation and migration of oral squamous cell carcinoma cells by targeting DKK. Biochem Cell Biol. 2018;96(3):355-64.
Li MM, Chen X, Chen L, Chen K, Zhou JY, Song JP. MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM. J Transl Med. 2018;16(1):161.
Sysol JR, Chen JW, Singla S, Zhao SP, Comhair S, Natarajan V, Machado RF. Micro-RNA-1 is decreased by hypoxia and contributes to the development of pulmonary vascular remodeling via regulation of sphingosine kinase 1. Am J Physiol Lung Cell Mol Physiol. 2018;314(3):L461-72.
Liu K, Ying Z, Xia QX, Shi Y, Tang Q. MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1. Int J Mol Med. 2015;36(3): 817-24.
Chen J, Yin H, Jiang YL, Radhakrishnan SK, Huang ZP, Li JJ, Shi Z, Kilsdonk EP, Gui Y, Wang DZ, Zheng XL. Induction of microRNA-1 by myocardin in smooth muscle cells inhibits cell proliferation. Arterioscler Thromb Vasc Biol. 2011;31(2):368-75.
Tan JJ, Yang LG, Liu CC, Yan ZQ. MicroRNA-26a targets MAPK6 to inhibit smooth muscle cell proliferation and vein graft neointimal hyperplasia. Sci Rep. 2017;7:46602.
Albinsson S, Swärd K. Targeting smooth muscle microRNAs for therapeutic benefit in vascular disease. Pharmacol Res. 2013;75:28-36.
Solly EL, Dimasi CG, Bursill CA, Psaltis PJ, Tan JTM. MicroRNAs as therapeutic targets and clinical biomarkers in atherosclerosis. J Clin Med. 2019;8(12):2199.
Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling. Biomed Res Int. 2015;2015:354517.
Vacante F, Denby L, Sluimer JC, Baker AH. The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease. Vascul Pharmacol. 2019;112:24-30.
Song JT, Hu B, Qu HY, Bi CL, Huang XZ, Zhang M. Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells. PLoS One. 2012;7(10):e47657.
Li SM, Wu HL, Yu X, Tang K, Wang SG, Ye ZQ, Hu J. The putative tumour suppressor miR-1-3p modulates prostate cancer cellaggressiveness by repressing E2F5 and PFTK1. J Exp Clin Cancer Res. 2018;37(1):219.
Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo MA, Cimino V, De Marinis L, Frustaci A, Catalucci D, Condorelli G. Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation. 2009;120(23):2377-85.
Shiu YT, Jaimes EA. Transcription Factor ETS-1 and Reactive Oxygen Species: Role in Vascular and Renal Injury. Antioxidants (Basel). 2018;7(7):84.
Hao GH, Han ZH, Meng Z, Wei J, Gao DF, Zhang H, Wang NP. Ets-1 upregulation mediates angiotensin II-related cardiac fibrosis. Int J Clin Exp Patho. 2015;8(9):10216-27.
Zhan YM, Brown C, Maynard EM, Anshelevich A, Ni WH, Ho IC, Oettgen P. Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling. J Clin Invest. 2005;115(9):2508-16.
Zhang C, Kavurma MM, Lai A, Khachigian LM. Ets-1 protects vascular smooth muscle cells from undergoing apoptosis by activating p21WAF1/Cip1: ETS-1 regulates basal and and inducible p21WAF1/Cip: ETS-1 regulates basal and inducible p21WAF1/Cip1 transcription via distinct cis-acting elements in the p21WAF/Cip1 promoter. J Biol Chem. 2003;278(30):27903-9.
Aoki T, Kataoka H, Nishimura M, R Ishibashi R, Morishita R, Miyamoto S. Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells. Gene Ther. 2010;17(9):1117-23.
Feng WG, Xing DQ, Hua P, Zhang Y, Chen YF, Oparil S, Jaimes EA. The transcription factor ETS-1 mediates proinflammatory responses and neointima formation in carotid artery endoluminal vascular injury. Hypertension. 2010;55(6):1381-8.
Wang YS, Cao W, Cui JJ, Yu Y, Zhao YB, Jian Shi J, Wu J, Xia ZY, Yu B, Liu JJ. Arterial Wall Stress Induces Phenotypic Switching of Arterial Smooth Muscle Cells in Vascular Remodeling by Activating the YAP/TAZ Signaling Pathway. Cell Physiol Biochem. 2018;51(2):842-53.
Liu XX, Huang XZ, Chen L, Zhang Y, Li MM, Wang L, Ge C Wang H, Zhang M. Mechanical stretch promotes matrix metalloproteinase-2 and prolyl-4-hydroxylase α1 production in human aortic smooth muscle cells via Akt-p38 MAPK-JNK signaling. Int J Biochem Cell Biol. 2015;62:15-23.
Zhou N, Zhang Y, Wang T, He JY, He HZ, He LC. The imperatorin derivative OW1, a new vasoactive compound, inhibits VSMC proliferation and extracellular matrix hyperplasia. Toxicol Appl Pharmacol. 2015;284(2):125–33.
Wahart A, Hocine T, Albrecht C, Henry A, Sarazin T, Martiny L, El Btaouri H, Maurice P, Bennasroune A, Romier-Crouzet B, Blaise S, Duca L. Role of elastin peptides and elastin receptor complex in metabolic and cardiovascular diseases. FEBS J. 2019;286(15):2980-93.
Dandré F, Owens GK. Platelet-derived growth factor-BB and Ets-1 transcription factor negatively regulate transcription of multiple smooth muscle cell differentiation marker genes. Am J Physiol Heart Circ Physiol. 2004;286(6):H2042-51.
Wang JG, Zhao XG, Wang XL, Liu MX, Wan W. Low expression of miR-1 promotes osteogenic repair of bone marrow mesenchymal stem cells by targeting TLR1. Eur Rev Med Pharmacol Sci. 2020;24(7):3492-500.
Rao VH, Rai V, Stoupa S, Agrawal DK. Blockade of Ets-1 attenuates epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells. Am J Physiol Heart Circ Physiol. 2015;309(6):H1075-86.
Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960-75.
Chiu CZ, Wang BW, Shyu KG. Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells. J Biomed Sci. 2013;20(1):50.
Wang BW, Chang H, Shyu KG. Regulation of resistin by cyclic mechanical stretch in cultured rat
vascular smooth muscle cells. Clin Sci (Lond). 2009; 118(3):221-30.
Gang Liu G, Hitomi H, Hosomi N, Bai Lei B, Pelisch N, Nakano D, Kiyomoto H, Hong Ma H, Nishiyama A. Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells. Hypertens Res. 2010;33(12):1250-7.
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