Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

Authors

  • Lei Li The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515
  • Yilin Xie School of Life Science and Biotechnology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University, Shanghai, 200240
  • Li Shen The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515
  • Juanjuan Tan School of Life Science and Biotechnology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University, Shanghai, 200240
  • Yingchun Qin Shanghai University of Traditional Chinese Medicine, Shanghai, 200240
  • Zhiqiang Yan 1. The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515; 2. Central Laboratory, Fengxian Hospital affiliated to Southern Medical University, Shanghai, 201499

Keywords:

cytoglobin, vascular smooth muscle cells, hypertension, cell migration, cell proliferation

Abstract

Paper description:

  • Cytoglobin is involved in injury-induced vascular remodeling.
  • Decreased expression of cytoglobin was detected in the aorta of hypertensive rats compared to normotensive rats.
  • Cytoglobin overexpression was capable of promoting proliferation and migration of vascular smooth muscle cells, and altering the expression of extracellular matrix components.
  • Cytoglobin could play a role in pathological vascular remodeling.


Abstract: Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling.

https://doi.org/10.2298/ABS191024009L

Received: October 24, 2019; Revised: February 15, 2020; Accepted: February 24, 2020; Published online: February 26, 2020

How to cite this article: Li L, Xie Y, Shen L, Tan J, Qin Y, Yan Z. Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells. Arch Biol Sci. 2020;72(2):165-72.

 

Downloads

Download data is not yet available.

References

Lackland DT, Weber MA. Global burden of cardiovascular disease and stroke: hypertension at the core. Can J Cardiol. 2015;31(5):569-71.

Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC. Vascular smooth muscle contraction in hypertension. Cardiovasc Res. 2018;114(4):529-39.

Schiffrin EL. Vascular remodeling in hypertension: mechanisms and treatment. Hypertension. 2012;59(2):367-74.

Savoia C, Burger D, Nishigaki N, Montezano A, Touyz RM. Angiotensin II and the vascular phenotype in hypertension. Expert Rev Mol Med. 2011;13:e11.

Intengan HD, Schiffrin EL. Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension. 2000;36(3):312-8.

Montezano AC, Tsiropoulou S, Dulak-Lis M, Harvey A, Camargo Lde L, Touyz RM. Redox signaling, Nox5 and vascular remodeling in hypertension. Curr Opin Nephrol Hypertens. 2015;24(5):425-33.

Coll-Bonfill N, de la Cruz-Thea B, Pisano MV, Musri MM. Noncoding RNAs in smooth muscle cell homeostasis: implications in phenotypic switch and vascular disorders. Pflugers Arch. 2016;468(6):1071-87.

Brown IAM, Diederich L, Good ME, DeLalio LJ, Murphy SA, Cortese-Krott MM, Hall JL, Le TH, Isakson BE. Vascular Smooth Muscle Remodeling in Conductive and Resistance Arteries in Hypertension. Arterioscler Thromb Vasc Biol. 2018;38(9):1969-85.

Tuna BG, Bakker EN, VanBavel E. Smooth muscle biomechanics and plasticity: relevance for vascular calibre and remodelling. Basic Clin Pharmacol Toxicol. 2012;110(1):35-41.

Ma KT, Li XZ, Li L, Jiang XW, Chen XY, Liu WD, Zhao L, Zhang ZS, Si JQ. Role of gap junctions in the contractile response to agonists in the mesenteric artery of spontaneously hypertensive rats. Hypertens Res. 2014;37(2):110-5.

Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K. Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem. 2001;276(27):25318-23.

Shigematsu A, Adachi Y, Matsubara J, Mukaide H, Koike-Kiriyama N, Minamino K, Shi M, Yanai S, Imamura M, Taketani S, Ikehara S. Analyses of expression of cytoglobin by immunohistochemical studies in human tissues. Hemoglobin. 2008;32(3):287-96.

Latina A, Viticchie G, Lena AM, Piro MC, Annicchiarico-Petruzzelli M, Melino G, Candi E. DeltaNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer. Oncogene. 2016;35(12):1493-503.

Rowland LK, Campbell PS, Mavingire N, Wooten JV, McLean L, Zylstra D, Thorne G, Daly D, Boyle K, Whang S, Unternaehrer J, Brantley EJ. Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand-mediated triple negative breast cancer cell death. J Cell Biochem. 2019;120(4):6004-14.

Jourd'heuil FL, Xu H, Reilly T, McKellar K, El Alaoui C, Steppich J, Liu YF, Zhao W, Ginnan R, Conti D, Lopez-Soler R, Asif A, Keller RK, Schwarz JJ, Thanh Thuy LT, Kawada N, Long X, Singer HA, Jourd'heuil D. The Hemoglobin Homolog Cytoglobin in Smooth Muscle Inhibits Apoptosis and Regulates Vascular Remodeling. Arterioscler Thromb Vasc Biol. 2017;37(10):1944-55.

Nishi H, Inagi R, Kawada N, Yoshizato K, Mimura I, Fujita T, Nangaku M. Cytoglobin, a novel member of the globin family, protects kidney fibroblasts against oxidative stress under ischemic conditions. Am J Pathol. 2011;178(1):128-39.

Zhang S, Li X, Jourd'heuil FL, Qu S, Devejian N, Bennett E, Jourd'heuil D, Cai C. Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFkappaB/iNOS Signal Pathway and Nitric Oxide Production. Sci Rep. 2017;7(1):10754.

Liu X, El-Mahdy MA, Boslett J, Varadharaj S, Hemann C, Abdelghany TM, Ismail RS, Little SC, Zhou D, Thuy LT, Kawada N, Zweier JL. Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall. Nat Commun. 2017;8:14807.

Lilly B, Dammeyer K, Marosis S, McCallinhart PE, Trask AJ, Lowe M, Sawant D. Endothelial cell-induced cytoglobin expression in vascular smooth muscle cells contributes to modulation of nitric oxide. Vascul Pharmacol. 2018;110:7-15.

Ray JL, Leach R, Herbert JM, Benson M. Isolation of vascular smooth muscle cells from a single murine aorta. Methods Cell Sci. 2001;23(4):185-8.

Jiang L, Wang D, Zhang Y, Li J, Wu Z, Wang Z, Wang D. Investigation of the pro-apoptotic effects of arbutin and its acetylated derivative on murine melanoma cells. Int J Mol Med. 2018;41(2):1048-54.

Alexander MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol. 2012;74:13-40.

Chaulet H, Desgranges C, Renault MA, Dupuch F, Ezan G, Peiretti F, Loirand G, Pacaud P, Gadeau AP. Extracellular nucleotides induce arterial smooth muscle cell migration via osteopontin. Circ Res. 2001;89(9):772-8.

Wang YT, Chen J, Li X, Umetani M, Chen Y, Li PL, Zhang Y. Contribution of transcription factor EB to adipoRon-induced inhibition of arterial smooth muscle cell proliferation and migration. Am J Physiol Cell Physiol. 2019;317(5):C1034-C47.

Castro MM, Rizzi E, Ceron CS, Guimaraes DA, Rodrigues GJ, Bendhack LM, Gerlach RF, Tanus-Santos JE. Doxycycline ameliorates 2K-1C hypertension-induced vascular dysfunction in rats by attenuating oxidative stress and improving nitric oxide bioavailability. Nitric Oxide. 2012;26(3):162-8.

Demirci S, Dogan A, Apdik H, Tuysuz EC, Gulluoglu S, Bayrak OF, Sahin F. Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells. Mol Cell Biochem. 2018;437(1-2):133-42.

Feng Y, Wu M, Li S, He X, Tang J, Peng W, Zeng B, Deng C, Ren G, Xiang T. The epigenetically downregulated factor CYGB suppresses breast cancer through inhibition of glucose metabolism. J Exp Clin Cancer Res. 2018;37(1):313.

Oleksiewicz U, Liloglou T, Tasopoulou KM, Daskoulidou N, Bryan J, Gosney JR, Field JK, Xinarianos G. Cytoglobin has bimodal: tumour suppressor and oncogene functions in lung cancer cell lines. Hum Mol Genet. 2013;22(16):3207-17.

Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004;84(3):767-801.

Bennett MR, Sinha S, Owens GK. Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res. 2016;118(4):692-702.

Zhang Y-n, Xie B-d, Sun L, Chen W, Jiang S-L, Liu W, Bian F, Tian H, Li R-K. Phenotypic switching of vascular smooth muscle cells in the ‘normal region’ of aorta from atherosclerosis patients is regulated bymiR-145. Journal of Cellular and Molecular Medicine. 2016;20(6):1049-61.

Strzalka W, Ziemienowicz A. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation. Ann Bot. 2011;107(7):1127-40.

Liu Y, Zhang J, Yi B, Chen M, Qi J, Yin Y, Lu X, Jasmin JF, Sun J. Nur77 suppresses pulmonary artery smooth muscle cell proliferation through inhibition of the STAT3/Pim-1/NFAT pathway. Am J Respir Cell Mol Biol. 2014;50(2):379-88.

Thi Thanh Hai N, Thuy LTT, Shiota A, Kadono C, Daikoku A, Hoang DV, Dat NQ, Sato-Matsubara M, Yoshizato K, Kawada N. Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice. Sci Rep. 2018;8(1):17860.

Wei H, Lin L, Zhang X, Feng Z, Wang Y, You Y, Wang X, Hou Y. Effect of cytoglobin overexpression on extracellular matrix component synthesis in human tenon fibroblasts. Biol Res. 2019;52(1):23.

Downloads

Published

2020-07-01

How to Cite

1.
Li L, Xie Y, Shen L, Tan J, Qin Y, Yan Z. Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells. Arch Biol Sci [Internet]. 2020Jul.1 [cited 2024Nov.22];72(2):165-72. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/4726

Issue

Section

Articles