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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Alleviation of Angiotensin II-Induced Vascular Endothelial Cell Injury Through Long Non-coding RNA TUG1 Inhibition

Author(s): Lin Shi, Hui Li, Lingzhi Sun, Caijun Tian and Haitao Li*

Volume 27, Issue 10, 2024

Published on: 10 October, 2023

Page: [1523 - 1532] Pages: 10

DOI: 10.2174/0113862073265220231004071645

Price: $65

Abstract

Background: Hypertension damages endothelial cells, causing vascular remodelling. It is caused by Ang II-induced endothelial cell (EC) destruction. The long noncoding RNA (lncRNAs) are emerging regulators of endothelium homeostasis. Injured endothelium expresses lncRNA taurine-upregulated gene 1 (TUG1), which may mediate endothelial cell damage, proliferation, apoptosis, and autophagy and contribute to cardiovascular disease. However, uncertainty surrounds the function of lncRNA TUG1, on arterial endothelium cell damage.

Objective: This research aimed to investigate the role and mechanism of lncRNA TUG1 in vascular endothelial cell injury.

Method: A microarray analysis of lncRNA human gene expression was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVEC) cultures. The viability, apoptosis, and migration of Ang II-treated HUVECs were then evaluated. In order to investigate the role of lncRNA TUG1 in hypertension, qRT-PCR, western blotting, and RNA-FISH were used to examine the expression of TUG1 in SHR mice.

Results: Ang II-activated HUVECs and SHR rats' abdominal aortas highly express the lncRNA TUG1. LncRNA TUG1 knockdown in HUVECs could increase cell viability, reduce apoptosis, and produce inflammatory factors. In SHR rat abdominal aortas, lncRNA TUG1 knockdown promoted proliferation and inhibited apoptosis. HE spotting showed that lncRNA TUG1 knockdown improved SHR rats' abdominal aorta shape. lncRNA TUG1 knockdown promotes miR-9- 5p, which inhibits CXCR4 following transcription. The lncRNA TUG1/miR-9-5p/CXCR4 axis and vascular cell injury were also examined. MiR-9-5p silencing or CXCR4 overexpression lowered cell survival, apoptosis, and lncRNA TUG1-induced IL-6 and NO expression.

Conclusion: lncRNA TUG1 suppression could reduce Ang II-induced endothelial cell damage by regulating and targeting miR-9-5p to limit CXCR4 expression and open new vascular disease research pathways.

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[1]
Siddiqui, M.A.; Mittal, P.K.; Little, B.P.; Miller, F.H.; Akduman, E.I.; Ali, K.; Sartaj, S.; Moreno, C.C. Secondary hypertension and complications: diagnosis and role of imaging. Radiographics, 2019, 39(4), 1036-1055.
[http://dx.doi.org/10.1148/rg.2019180184] [PMID: 31173541]
[2]
Iadecola, C.; Davisson, R.L. Hypertension and cerebrovascular dysfunction. Cell Metab., 2008, 7(6), 476-484.
[http://dx.doi.org/10.1016/j.cmet.2008.03.010] [PMID: 18522829]
[3]
Kario, K.; Eguchi, K.; Hoshide, S.; Hoshide, Y.; Umeda, Y.; Mitsuhashi, T.; Shimada, K. U-curve relationship between orthostatic blood pressure change and silent cerebrovascular disease in elderly hypertensives. J. Am. Coll. Cardiol., 2002, 40(1), 133-141.
[http://dx.doi.org/10.1016/S0735-1097(02)01923-X] [PMID: 12103267]
[4]
Guo, J.; Wang, Z.; Wu, J.; Liu, M.; Li, M.; Sun, Y.; Huang, W.; Li, Y.; Zhang, Y.; Tang, W.; Li, X.; Zhang, C.; Hong, F.; Li, N.; Nie, J.; Yi, F. Endothelial sirt6 is vital to prevent hypertension and associated cardiorenal injury through targeting Nkx3.2-GATA5 signaling. Circ. Res., 2019, 124(10), 1448-1461.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.314032] [PMID: 30894089]
[5]
Montezano, A.C.; Nguyen Dinh Cat, A.; Rios, F.J.; Touyz, R.M. Angiotensin II and vascular injury. Curr. Hypertens. Rep., 2014, 16(6), 431.
[http://dx.doi.org/10.1007/s11906-014-0431-2] [PMID: 24760441]
[6]
Zhang, H.; Xu, Q.; Thakur, A.; Alfred, M.O.; Chakraborty, M.; Ghosh, A.; Yu, X. Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs. Life Sci., 2018, 213, 258-268.
[http://dx.doi.org/10.1016/j.lfs.2018.10.028] [PMID: 30342074]
[7]
Prestes, P.R.; Maier, M.C.; Woods, B.A.; Charchar, F.J. A guide to the short, long and circular rnas in hypertension and cardiovascular disease. Int. J. Mol. Sci., 2020, 21(10), 3666.
[http://dx.doi.org/10.3390/ijms21103666] [PMID: 32455975]
[8]
Yao, Q.P.; Xie, Z.W.; Wang, K.X.; Zhang, P.; Han, Y.; Qi, Y.X.; Jiang, Z.L. Profiles of long noncoding RNAs in hypertensive rats. J. Hypertens., 2017, 35(6), 1195-1203.
[http://dx.doi.org/10.1097/HJH.0000000000001304] [PMID: 28319593]
[9]
Bayoglu, B.; Yuksel, H.; Cakmak, H.A.; Dirican, A.; Cengiz, M. Polymorphisms in the long non-coding RNA CDKN2B-AS1 may contribute to higher systolic blood pressure levels in hypertensive patients. Clin. Biochem., 2016, 49(10-11), 821-827.
[http://dx.doi.org/10.1016/j.clinbiochem.2016.02.012] [PMID: 26944720]
[10]
Teng, W.; Qiu, C.; He, Z.; Wang, G.; Xue, Y.; Hui, X. Linc00152 suppresses apoptosis and promotes migration by sponging miR-4767 in vascular endothelial cells. Oncotarget, 2017, 8(49), 85014-85023.
[http://dx.doi.org/10.18632/oncotarget.18777] [PMID: 29156700]
[11]
Lu, W.; Huang, S.Y.; Su, L.; Zhao, B.X.; Miao, J.Y. Long noncoding RNA LOC100129973 suppresses apoptosis by targeting miR-4707-5p and miR-4767 in vascular endothelial cells. Sci. Rep., 2016, 6(1), 21620.
[http://dx.doi.org/10.1038/srep21620] [PMID: 26887505]
[12]
Wang, J.; Chen, L.; Li, H.; Yang, J.; Gong, Z.; Wang, B.; Zhao, X. Clopidogrel reduces apoptosis and promotes proliferation of human vascular endothelial cells induced by palmitic acid via suppression of the long non-coding RNA HIF1A-AS1 in vitro. Mol. Cell. Biochem., 2015, 404(1-2), 203-210.
[http://dx.doi.org/10.1007/s11010-015-2379-1] [PMID: 25761653]
[13]
Zheng, J.; Hu, L.; Cheng, J.; Xu, J.; Zhong, Z.; Yang, Y.; Yuan, Z. lncRNA PVT1 promotes the angiogenesis of vascular endothelial cell by targeting miR 26b to activate CTGF/ANGPT2. Int. J. Mol. Med., 2018, 42(1), 489-496.
[http://dx.doi.org/10.3892/ijmm.2018.3595] [PMID: 29620147]
[14]
Shi, L.; Tian, C.; Sun, L.; Cao, F.; Meng, Z. The lncRNA TUG1/miR-145-5p/FGF10 regulates proliferation and migration in VSMCs of hypertension. Biochem. Biophys. Res. Commun., 2018, 501(3), 688-695.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.049] [PMID: 29758198]
[15]
Du, S.S.; Zuo, X.J.; Xin, Y.; Man, J.X.; Wu, Z.L. Expression of lncRNA TUG1 in hypertensive patients and its relationship with change state of an illness. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(2), 870-877.
[PMID: 32016993]
[16]
Su, Q.; Liu, Y.; Lv, X.W.; Ye, Z.L.; Sun, Y.H.; Kong, B.H.; Qin, Z.B. Inhibition of lncRNA TUG1 upregulates miR-142-3p to ameliorate myocardial injury during ischemia and reperfusion via targeting HMGB1- and Rac1-induced autophagy. J. Mol. Cell. Cardiol., 2019, 133, 12-25.
[http://dx.doi.org/10.1016/j.yjmcc.2019.05.021] [PMID: 31145943]
[17]
Guo, C.; Qi, Y.; Qu, J.; Gai, L.; Shi, Y.; Yuan, C. Pathophysiological functions of the lncRNA TUG1. Curr. Pharm. Des., 2020, 26(6), 688-700.
[http://dx.doi.org/10.2174/1381612826666191227154009] [PMID: 31880241]
[18]
Duan, W.; Nian, L.; Qiao, J.; Liu, N.N. LncRNA TUG1 aggravates the progression of cervical cancer by binding PUM2. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(19), 8211-8218.
[PMID: 31646551]
[19]
Dhiman, A.; Sharma, R.; Singh, R.K. Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021). Acta Pharm. Sin. B, 2022, 12(7), 3006-3027.
[http://dx.doi.org/10.1016/j.apsb.2022.03.021] [PMID: 35865090]
[20]
Yu, C.; Li, L.; Xie, F.; Guo, S.; Liu, F.; Dong, N.; Wang, Y. LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc. Res., 2018, 114(1), 168-179.
[http://dx.doi.org/10.1093/cvr/cvx180] [PMID: 29016735]
[21]
Li, F.P.; Lin, D.Q.; Gao, L.Y. LncRNA TUG1 promotes proliferation of vascular smooth muscle cell and atherosclerosis through regulating miRNA-21/PTEN axis. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(21), 7439-7447.
[PMID: 30468492]
[22]
Gao, N.; Li, Y.; Li, J.; Gao, Z.; Yang, Z.; Li, Y.; Liu, H.; Fan, T. Long non-coding RNAs: The regulatory mechanisms, research strategies, and future directions in cancers. Front. Oncol., 2020, 10, 598817.
[http://dx.doi.org/10.3389/fonc.2020.598817] [PMID: 33392092]
[23]
Young, T.L.; Matsuda, T.; Cepko, C.L. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr. Biol., 2005, 15(6), 501-512.
[http://dx.doi.org/10.1016/j.cub.2005.02.027] [PMID: 15797018]
[24]
Gimbel, A.T.; Koziarek, S.; Theodorou, K. Aging-regulated TUG1 is dispensable for endothelial cell function. PLoS One, 2022, 17(9), e0265160.
[http://dx.doi.org/10.1371/journal.pone.0265160]
[25]
Jayasuriya, R.; Ganesan, K.; Xu, B.; Ramkumar, K.M. Emerging role of long non-coding RNAs in endothelial dysfunction and their molecular mechanisms. Biomed. Pharmacother., 2022, 145, 112421.
[http://dx.doi.org/10.1016/j.biopha.2021.112421] [PMID: 34798473]
[26]
Toshner, M.; Rothman, A. IL-6 in pulmonary hypertension: Why novel is not always best. Eur. Respir. J., 2020, 55(4), 2000314.
[http://dx.doi.org/10.1183/13993003.00314-2020] [PMID: 32300021]
[27]
Chou, C.H.; Hung, C.S.; Liao, C.W.; Wei, L.H.; Chen, C.W.; Shun, C.T.; Wen, W.F.; Wan, C.H.; Wu, X.M.; Chang, Y.Y.; Wu, V.C.; Wu, K.D.; Lin, Y.H. IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis. Cardiovasc. Res., 2018, 114(5), 690-702.
[http://dx.doi.org/10.1093/cvr/cvy013] [PMID: 29360942]
[28]
Zhang, Y.D. Ding, X.J.; Dai, H.Y.; Peng, W.S.; Guo, N.F.; Zhang, Y.; Zhou, Q.L.; Chen, X.L. SB-216763, a GSK‐3β inhibitor, protects against aldosterone-induced cardiac, and renal injury by activating autophagy. J. Cell. Biochem., 2018, 119(7), 5934-5943.
[http://dx.doi.org/10.1002/jcb.26788] [PMID: 29600538]
[29]
Kumari, A.; Silakari, O.; Singh, R.K. Recent advances in colony stimulating factor-1 receptor/c-FMS as an emerging target for various therapeutic implications. Biomed. Pharmacother., 2018, 103, 662-679.
[http://dx.doi.org/10.1016/j.biopha.2018.04.046] [PMID: 29679908]
[30]
Yao, Y.; Chang, W.; Jin, Y. Association between TNF-a promoter -308G/A polymorphism and essential hypertension in the Asian population: A meta-analysis. J. Renin Angiotensin Aldosterone Syst., 2017, 18(4)
[http://dx.doi.org/10.1177/1470320317741066] [PMID: 29258412]
[31]
Kumar, S.; Singh, R.K.; Bhardwaj, T.R. Therapeutic role of nitric oxide as emerging molecule. Biomed. Pharmacother., 2017, 85, 182-201.
[http://dx.doi.org/10.1016/j.biopha.2016.11.125] [PMID: 27940398]
[32]
Korsager Larsen, M.; Matchkov, V.V. Hypertension and physical exercise: The role of oxidative stress. Medicina, 2016, 52(1), 19-27.
[http://dx.doi.org/10.1016/j.medici.2016.01.005] [PMID: 26987496]
[33]
Pinheiro, L.C.; Tanus-Santos, J.E.; Castro, M.M. The potential of stimulating nitric oxide formation in the treatment of hypertension. Expert Opin. Ther. Targets, 2017, 21(5), 543-556.
[http://dx.doi.org/10.1080/14728222.2017.1310840] [PMID: 28338370]
[34]
Gkaliagkousi, E.; Douma, S.; Zamboulis, C.; Ferro, A. Nitric oxide dysfunction in vascular endothelium and platelets: Role in essential hypertension. J. Hypertens., 2009, 27(12), 2310-2320.
[http://dx.doi.org/10.1097/HJH.0b013e328330e89a] [PMID: 19838132]
[35]
Lahera, V.; de las Heras, N.; López-Farré, A.; Manucha, W.; Ferder, L. Role of mitochondrial dysfunction in hypertension and obesity. Curr. Hypertens. Rep., 2017, 19(2), 11.
[http://dx.doi.org/10.1007/s11906-017-0710-9] [PMID: 28233236]
[36]
Togliatto, G.; Lombardo, G.; Brizzi, M.F. The future challenge of Reactive Oxygen Species (ROS) in hypertension: From bench to bed side. Int. J. Mol. Sci., 2017, 18(9), 1988.
[http://dx.doi.org/10.3390/ijms18091988] [PMID: 28914782]
[37]
Bonnet, S.; Boucherat, O. The ROS controversy in hypoxic pulmonary hypertension revisited. Eur. Respir. J., 2018, 51(3), 1800276.
[http://dx.doi.org/10.1183/13993003.00276-2018] [PMID: 29519907]
[38]
Senoner, T.; Dichtl, W. Oxidative stress in cardiovascular diseases: Still a therapeutic target? Nutrients, 2019, 11(9), 2090.
[http://dx.doi.org/10.3390/nu11092090] [PMID: 31487802]
[39]
Aggarwal, S.; Gross, C.M.; Sharma, S.; Fineman, J.R.; Black, S.M. Reactive oxygen species in pulmonary vascular remodeling. Compr. Physiol., 2013, 3(3), 1011-1034.
[http://dx.doi.org/10.1002/cphy.c120024] [PMID: 23897679]
[40]
You, G.; Long, X.; Song, F.; Huang, J.; Tian, M.; Xiao, Y.; Deng, S.; Wu, Q. Metformin activates the AMPK-mTOR pathway by modulating lncRNA TUG1 to induce autophagy and inhibit atherosclerosis. Drug Des. Devel. Ther., 2020, 14, 457-468.
[http://dx.doi.org/10.2147/DDDT.S233932] [PMID: 32099330]
[41]
Chen, C.; Cheng, G.; Yang, X.; Li, C.; Shi, R.; Zhao, N. Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a. Am. J. Transl. Res., 2016, 8(7), 2981-2991.
[PMID: 27508018]
[42]
Teicher, B.A.; Fricker, S.P. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin. Cancer Res., 2010, 16(11), 2927-2931.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2329] [PMID: 20484021]
[43]
Jiang, X.; Wang, C.; Fitch, S.; Yang, F. Targeting tumor hypoxia using nanoparticle-engineered CXCR4-overexpressing adipose-derived stem cells. Theranostics, 2018, 8(5), 1350-1360.
[http://dx.doi.org/10.7150/thno.22736] [PMID: 29507625]
[44]
Lu, J.; Zhou, W.H.; Ren, L.; Zhang, Y.Z. CXCR4, CXCR7, and CXCL12 are associated with trophoblastic cells apoptosis and linked to pathophysiology of severe preeclampsia. Exp. Mol. Pathol., 2016, 100(1), 184-191.
[http://dx.doi.org/10.1016/j.yexmp.2015.12.013] [PMID: 26721717]

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