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Vol. 66 No. 7: Issue 7

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Effects of miR-7 on Hcy-induced rat cerebral arterial vascular smooth muscle cell proliferation, migration and inflammatory factor expression by targeting MMP-14 to regulate TLR4/NF-κB signaling pathway

https://doi.org/10.14715/cmb/2020.66.7.3
Hongdan Ma
Department of Rehabilitation, Shenzhen Longgang Central Hospital, Shenzhen, 518116, China
Lei Wang
Department of Rehabilitation, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
Wen Lv
Department of Rehabilitation, Shenzhen Longgang Central Hospital, Shenzhen, 518116, China
Zheng Lv
Department of Rehabilitation, Shenzhen Longgang Central Hospital, Shenzhen, 518116, China

Corresponding Author(s) : Hongdan Ma

zhenglv242424@outlook.com

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7

Abstract

The current research aimed to investigate the effect of miR-7 targeting matrix metalloproteinase 14 (MMP-14) on homocysteine (Hcy)-induced rat cerebral artery vascular smooth muscle cells (VSMCs) proliferation, migration and inflammatory factor expression and its possible mechanism. The expression of miR-7 and MMP-14 in Hcy-induced VSMCs were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot. Methyl Thiazolyl Tetrazolium (MTT) method, Transwell assays and enzyme-linked immunosorbent assay (ELISA) were performed to detect the effect of miR-7 and MMP-14 expression on the proliferation and migration, as well as interleukin 6 (IL-6) and tumor necrosis factor ɑ (TNF-ɑ) expression of Hcy-induced VSMCs. The interaction between miR-7 and MMP-14 was detected by dual-luciferase reporter gene assay. Western blot was applied to analyse the effects of miR-7 and MMP-14 expression on the Toll-like receptor (TLR4)/nuclear transcription factor-KB (NF-κB) signaling pathway. The results showed that after induced by Hcy, the expression of miR-7 in VSMCs was significantly reduced, the expression of MMP-14 was significantly increased, and the cell viability, the number of migrating cells, IL-6 and TNF-ɑ expression were significantly increased (P<0.05). After overexpression of miR-7, the viability, migration cell numbers, IL-6 and TNF-ɑ expression of Hcy-induced VSMCs were significantly reduced (P<0.05). miR-7 directly binds to MMP-14 and negatively regulates the expression of MMP-14. After overexpression of miR-7, the levels of TLR4 and p-NF-κB p65 in VSMCs were significantly reduced (P<0.05); overexpression of MMP-14 could reduce the effect of miR-7 overexpression on TLR4 and p-NF-κB p65 expression in VSMCs (P<0.05). Overexpression of MMP-14 and/or activation of the TLR4/NF-κB signaling pathway could reverse the effect of miR-7 overexpression on the proliferation, migration and IL-6 and TNF-ɑ expression of Hcy-induced VSMCs (P<0.05). It is concluded that miR-7 can inhibit Hcy-induced rat cerebral artery VSMCs proliferation, migration, and inflammatory factor expression by targeting the regulation of MMP-14 expression and inhibiting the activation of the TLR4/NF-κB signaling pathway.

Keywords

miR-7 MMP-14 Homocysteine Vascular smooth muscle cells Proliferation Migration TLR4/NF-κB signaling pathway.
Ma, H., Wang, L., Lv, W., & Lv, Z. (2020). Effects of miR-7 on Hcy-induced rat cerebral arterial vascular smooth muscle cell proliferation, migration and inflammatory factor expression by targeting MMP-14 to regulate TLR4/NF-κB signaling pathway. Cellular and Molecular Biology, 66(7), 12–17. https://doi.org/10.14715/cmb/2020.66.7.3
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References
  1. Gao S, Xu L, Zhang Y, et al. Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling. Cell Physiol Biochem, 2018; 50(5): 1740-1753.
  2. Lu Y, Thavarajah T, Gu W, et al. Impact of miRNA in Atherosclerosis. Arterioscler Thromb Vasc Biol, 2018; 38(9): e159-e170.
  3. Feinberg MW, Moore KJ. MicroRNA Regulation of Atherosclerosis. Circ Res, 2016, 118(4): 703-720.
  4. Kim T, Mehta SL, Morris-Blanco KC, et al. The microRNA miR-7a-5p ameliorates ischemic brain damage by repressing α-synuclein. Sci Signal. 2018; 11(560): eaat4285.
  5. Johnson JL, Jenkins NP, Huang WC, et al. Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability. Mediators Inflamm, 2014; 2014: 276457.
  6. Duan H, Li Y, Yan L, et al. MicroRNA-217 suppresses homocysteine-induced proliferation and migration of vascular smooth muscle cells via N-methyl-D-aspartic acid receptor inhibition. Clin Exp Pharmacol Physiol, 2016; 43(10): 967-975.
  7. Meng L, Liu L, Zhou C, et al. Polyphenols and Polypeptides in Chinese Rice Wine Inhibit Homocysteine-induced Proliferation and Migration of Vascular Smooth Muscle Cells. J Cardiovasc Pharmacol, 2016; 67(6): 482-490.
  8. Liu Y, Chen Y, Tan L, et al. Linc00299/miR-490-3p/AURKA axis regulates cell growth and migration in atherosclerosis. Heart Vessels, 2019; 34(8): 1370-1380.
  9. Li M, Pan M, You C, et al. The Therapeutic Potential of miR-7 in Cancers. Mini Rev Med Chem, 2019; 19(20): 1707-1716.
  10. Zou L, Ma X, Lin S, et al. Long noncoding RNA-MEG3 contributes to myocardial ischemia-reperfusion injury through suppression of miR-7-5p expression. Biosci Rep, 2019; 39(8): BSR20190210.
  11. Qian H, Hu K, Xie M, et al. Intracerebroventricular injection of miR-7 inhibits secondary brain injury induced by intracerebral hemorrhage via EGFR/STAT3 pathway in rats. J Cell Mol Immunol, 2018; 34(2): 141-147.
  12. Liao XH, Xiang Y, Li H, et al. VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers. Sci Rep, 2017; 7(1): 2660.
  13. Li TJ, Chen YL, Gua CJ, et al. MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways. Int J Clin Exp Pathol, 2015; 8(9): 10375-10384.
  14. Song P, Zhou Y, Coughlan KA, et al. Adenosine monophosphate-activated protein kinase-α2 deficiency promotes vascular smooth muscle cell migration via S-phase kinase-associated protein 2 upregulation and E-cadherin downregulation. Arterioscler Thromb Vasc Biol, 2014; 34(10): e23.
  15. Qiu L, Xu C, Jiang H, et al. Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response. Biol Pharm Bull, 2019, 42(1): 34-42.
  16. Müller A, Krämer SD, Meletta R, et al. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability. Nucl Med Biol, 2014; 41(7): 562-569.
  17. Li C, Jin XP, Zhu M, et al. Positive association of MMP 14 gene polymorphism with vulnerable carotid plaque formation in a Han Chinese population. Scand J Clin Lab Invest, 2014; 74(3): 248-253.
  18. Di Gregoli K, Jenkins N, Salter R, et al. MicroRNA-24 regulates macrophage behavior and retards atherosclerosis. Arterioscler Thromb Vasc Biol, 2014; 34(9): 1990-2000.
  19. Rocha DM, Caldas AP, Oliveira LL, et al. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis, 2016, 244(1): 211-215.
  20. Song Y, Hou M, Li Z, et al. TLR4/NF-κB/Ceramide signaling contributes to Ox-LDL-induced calcification of human vascular smooth muscle cells. Eur J Pharmacol, 2017; 794(1): 45-51.
  21. Lou X, Yu Z, Yang X, et al. Protective effect of rivaroxaban on arteriosclerosis obliterans in rats through modulation of the toll-like receptor 4/NF-κB signaling pathway. Exp Ther Med, 2019; 18(3): 1619-1626.
  22. Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Mod Genet J 2020; 15(2): 75-92.
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