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

  • Авторлар: Shi L.1, Li H.2, Sun L.3, Tian C.1, Li H.1
  • Мекемелер:
    1. Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
    2. Department of Emergency Internal Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
    3. Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicin
  • Шығарылым: Том 27, № 10 (2024)
  • Беттер: 1523-1532
  • Бөлім: Chemistry
  • URL: https://rjpbr.com/1386-2073/article/view/643841
  • DOI: https://doi.org/10.2174/0113862073265220231004071645
  • ID: 643841

Дәйексөз келтіру

Толық мәтін

Аннотация

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.

Авторлар туралы

Lin Shi

Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Hui Li

Department of Emergency Internal Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Lingzhi Sun

Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicin

Email: info@benthamscience.net

Caijun Tian

Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Haitao Li

Department of Internal Medicine-Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  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. doi: 10.1148/rg.2019180184 PMID: 31173541
  2. Iadecola, C.; Davisson, R.L. Hypertension and cerebrovascular dysfunction. Cell Metab., 2008, 7(6), 476-484. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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) doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1016/j.yexmp.2015.12.013 PMID: 26721717

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу

© Bentham Science Publishers, 2024