Docosahexaenoic acid inhibits vascular smooth muscle cell migration and proliferation by decreasing microRNA‑155 expression levels

Yin,Xiaoliang; Xu,Chunbo; Xu,Qiyang; Lang,Dehai

doi:10.3892/mmr.2020.11404

Docosahexaenoic acid inhibits vascular smooth muscle cell migration and proliferation by decreasing microRNA‑155 expression levels

Authors:
- Xiaoliang Yin
- Chunbo Xu
- Qiyang Xu
- Dehai Lang
View Affiliations

Affiliations: Department of Vascular Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China
Published online on: August 3, 2020 https://doi.org/10.3892/mmr.2020.11404
Pages: 3396-3404
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Vascular smooth muscle cell (VSMC) hyperplasia is a common cause of carotid restenosis. In the present study, the potential protective effects of docosahexaenoic acid (DHA) in carotid restenosis and the underlying mechanism of its effects were examined. VSMCs were treated with DHA, a polyunsaturated ω‑3 fatty acid. Cell migration and proliferation were assessed using wound healing and Cell Counting Kit‑8 assays and by measuring Ki‑67 protein levels. Additionally, the expression levels of microRNA‑155 were determined by reverse transcription‑quantitative PCR (RT‑qPCR). The involvement of microRNA‑155 in the regulation of migration and proliferation was evaluated by transfecting VSMCs with microRNA mimics and inhibitors. Moreover, the reversal of migration and proliferation after transfection of VSMCs with the microRNA mimics and subsequent treatment with DHA was investigated. A target gene of microRNA‑155 was identified using RT‑qPCR and luciferase assays. The migration and proliferation of VSMCs, as well as the expression of microRNA‑155 was inhibited by DHA stimulation. MicroRNA‑155 regulated the migration and proliferation of VSMCs. Finally, proliferation and migration of VSMCs were reduced following DHA treatment, which was mediated by an increase in the expression levels of microRNA‑155. Suppressor of cytokine signalling 1 (Socs1) was the target gene of microRNA‑155. In conclusion, DHA inhibited VSMC migration and proliferation by reducing microRNA‑155 expression. This effect may be caused by the microRNA‑155 target gene Socs1.

View Figures

View References

1	Bonati LH, Ederle J, Dobson J, Engelter S, Featherstone RL, Gaines PA, Beard JD, Venables GS, Markus HS, Clifton A, et al: Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy. Int J Stroke. 9:3396–305. 2014. View Article : Google Scholar
2	Plummer C, Henderson RD, O'Sullivan JD and Read SJ: Ischemic stroke and transient ischemic attack after head and neck radiotherapy: A review. Stroke. 42:2410–2418. 2011. View Article : Google Scholar : PubMed/NCBI
3	Schunck WH, Konkel A, Fischer R and Weylandt KH: Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases. Pharmacol Ther. 183:177–204. 2018. View Article : Google Scholar : PubMed/NCBI
4	Iverson C, Bacong A, Liu S, Baumgartner S, Lundstrom T, Oscarsson J and Miner JN: Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation. Sci Rep. 8:12172018. View Article : Google Scholar : PubMed/NCBI
5	Trattner S, Ruyter B, Ostbye TK, Kamal-Eldin A, Moazzami A, Pan J, Gjoen T, Brännäs E, Zlabek V and Pickova J: Influence of dietary sesamin, a bioactive compound on fatty acids and expression of some lipid regulating genes in Baltic Atlantic salmon (Salmo salar L.) juveniles. Physiol Res. 60:125–137. 2011. View Article : Google Scholar : PubMed/NCBI
6	Hirafuji M, Machida T, Tsunoda M, Miyamoto A and Minami M: Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells. Br J Pharmacol. 136:613–619. 2002. View Article : Google Scholar : PubMed/NCBI
7	Zhang J, Zhao F, Yu X, Lu X and Zheng G: MicroRNA-155 modulates the proliferation of vascular smooth muscle cells by targeting endothelial nitric oxide synthase. Int J Mol Med. 35:1708–1714. 2015. View Article : Google Scholar : PubMed/NCBI
8	Delbosc S, Glorian M, Le Port AS, Bereziat G, Andreani M and Limon I: The benefit of docosahexanoic acid on the migration of vascular smooth muscle cells is partially dependent on Notch regulation of MMP-2/-9. Am J Pathol. 172:1430–1440. 2008. View Article : Google Scholar : PubMed/NCBI
9	Terano T, Tanaka T, Tamura Y, Kitagawa M, Higashi H, Saito Y and Hirai A: Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex. Biochem Biophys Res Commun. 254:502–506. 1999. View Article : Google Scholar : PubMed/NCBI
10	Newell M, Baker K, Postovit LM and Field CJ: A critical review on the effect of docosahexaenoic acid (DHA) on cancer cell cycle progression. Int J Mol Sci. 18:17842017. View Article : Google Scholar
11	Rani K and Aung NY: Docosahexaenoic acid inhibits vascular smooth muscle cell proliferation induced by glucose variability. Open Biochem J. 11:56–65. 2017. View Article : Google Scholar : PubMed/NCBI
12	Oono K, Takahashi K, Sukehara S, Kurosawa H, Matsumura T, Taniguchi S and Ohta S: Inhibition of PC3 human prostate cancer cell proliferation, invasion and migration by eicosapentaenoic acid and docosahexaenoic acid. Mol Clin Oncol. 7:217–220. 2017.PubMed/NCBI
13	Geng L, Zhou W, Liu B, Wang X and Chen B: DHA induces apoptosis of human malignant breast cancer tissues by the TLR-4/PPAR-α pathways. Oncol Lett. 15:2967–2977. 2018.PubMed/NCBI
14	Sun Y, Wang K, Ye P, Wu J, Ren L, Zhang A, Huang X, Deng P, Wu C, Yue Z, et al: MicroRNA-155 promotes the directional migration of resident smooth muscle progenitor cells by regulating monocyte chemoattractant protein 1 in transplant arteriosclerosis. Arterioscler Thromb Vasc Biol. 36:1230–1239. 2016. View Article : Google Scholar : PubMed/NCBI
15	Li X, Kong D, Chen H, Liu S, Hu H, Wu T, Wang J, Chen W, Ning Y, Li Y and Lu Z: miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1. Sci Rep. 6:217892016. View Article : Google Scholar : PubMed/NCBI
16	Jin C, Cheng L, Lu X, Xie T, Wu H and Wu N: Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1. Mol Med Rep. 16:1584–1589. 2017. View Article : Google Scholar : PubMed/NCBI
17	Pacurari M and Tchounwou PB: Role of MicroRNAs in renin-angiotensin-aldosterone system-mediated cardiovascular inflammation and remodeling. Int J Inflam. 2015:1015272015. View Article : Google Scholar : PubMed/NCBI
18	Izzard L, Dlugolenski D, Xia Y, McMahon M, Middleton D, Tripp RA and Stambas J: Enhanced immunogenicity following miR-155 incorporation into the influenza a virus genome. Virus Res. 235:115–120. 2017. View Article : Google Scholar : PubMed/NCBI
19	Heymans S, Corsten MF, Verhesen W, Carai P, van Leeuwen RE, Custers K, Peters T, Hazebroek M, Stöger L, Wijnands E, et al: Macrophage microRNA-155 promotes cardiac hypertrophy and failure. Circulation. 128:1420–1432. 2013. View Article : Google Scholar : PubMed/NCBI
20	Bhattacharya S, Chalk AM, Ng AJ, Martin TJ, Zannettino AC, Purton LE, Lu J, Baker EK and Walkley CR: Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death. Oncogene. 35:5282–5294. 2016. View Article : Google Scholar : PubMed/NCBI
21	Ji Y, Wrzesinski C, Yu Z, Hu J, Gautam S, Hawk NV, Telford WG, Palmer DC, Franco Z, Sukumar M, et al: miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic gammac cytokines. Proc Natl Acad Sci USA. 112:476–481. 2015. View Article : Google Scholar : PubMed/NCBI
22	Kim S, Lee E, Jung J, Lee JW, Kim HJ, Kim J, Yoo HJ, Lee HJ, Chae SY, Jeon SM, et al: microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene. 37:2982–2991. 2018. View Article : Google Scholar : PubMed/NCBI
23	Yang LX, Liu G, Zhu GF, Liu H, Guo RW, Qi F and Zou JH: MicroRNA-155 inhibits angiotensin II-induced vascular smooth muscle cell proliferation. J Renin Angiotensin Aldosterone Syst. 15:109–116. 2014. View Article : Google Scholar : PubMed/NCBI
24	Zhang G, Zhong L, Luo H and Wang S: MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1. Onco Targets Ther. 12:7993–8002. 2019. View Article : Google Scholar : PubMed/NCBI
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
26	Wang CR, Zhu HF and Zhu Y: Knockout of microRNA-155 ameliorates the Th17/Th9 immune response and promotes wound healing. Curr Med Sci. 39:954–964. 2019. View Article : Google Scholar : PubMed/NCBI
27	Knolle MD, Chin SB, Rana BMJ, Englezakis A, Nakagawa R, Fallon PG, Git A and McKenzie ANJ: MicroRNA-155 protects group 2 innate lymphoid cells from apoptosis to promote type-2 immunity. Front Immunol. 9:22322018. View Article : Google Scholar : PubMed/NCBI
28	Saleh M, Friedl A, Srivastava M, Soliman H, Secombes CJ and El-Matbouli M: STAT3/SOCS3 axis contributes to the outcome of salmonid whirling disease. PLoS One. 15:e02344792020. View Article : Google Scholar : PubMed/NCBI
29	Oono K, Ohtake K, Watanabe C, Shiba S, Sekiya T and Kasono K: Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells. Lipids Health Dis. 19:152020. View Article : Google Scholar : PubMed/NCBI
30	Watanabe Y and Tatsuno I: Prevention of cardiovascular events with omega-3 polyunsaturated fatty acids and the mechanism involved. J Atheroscler Thromb. 27:183–198. 2020. View Article : Google Scholar : PubMed/NCBI
31	Farina FM, Hall IF, Serio S, Zani S, Climent M, Salvarani N, Carullo P, Civilini E, Condorelli G, Elia L and Quintavalle M: miR-128-3p is a novel regulator of vascular smooth muscle cell phenotypic switch and vascular diseases. Circ Res. 126:e120–e135. 2020. View Article : Google Scholar : PubMed/NCBI
32	Nakagawa I, Park HS, Yokoyama S, Wada T, Yamada S, Motoyama Y, Kichikawa K and Nakase H: Pretreatment with and ongoing use of omega-3 fatty acid ethyl esters reduce the slow-flow phenomenon and prevent in-stent restenosis in patients undergoing carotid artery stenting. J Vasc Surg. 66:122–129. 2017. View Article : Google Scholar : PubMed/NCBI
33	Ding X, Ge L, Yan A, Ding Y, Tao J, Liu Q and Qiao C: Docosahexaenoic acid serving as sensitizing agents and gefitinib resistance revertants in EGFR targeting treatment. Onco Targets Ther. 12:10547–10558. 2019. View Article : Google Scholar : PubMed/NCBI
34	Song TJ, Chang Y, Shin MJ, Heo JH and Kim YJ: Low levels of plasma omega 3-polyunsaturated fatty acids are associated with cerebral small vessel diseases in acute ischemic stroke patients. Nutr Res. 35:368–374. 2015. View Article : Google Scholar : PubMed/NCBI
35	Morin C, Rousseau E, Blier PU and Fortin S: Effect of docosahexaenoic acid monoacylglyceride on systemic hypertension and cardiovascular dysfunction. Am J Physiol Heart Circ Physiol. 309:H93–H102. 2015. View Article : Google Scholar : PubMed/NCBI
36	Yee D, Shah KM, Coles MC, Sharp TV and Lagos D: MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. J Biol Chem. 292:20683–20693. 2017. View Article : Google Scholar : PubMed/NCBI
37	Xu L and Leng H, Shi X, Ji J, Fu J and Leng H: miR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis. Biomed Pharmacother. 90:524–530. 2017. View Article : Google Scholar : PubMed/NCBI
38	Seok HY, Chen J, Kataoka M, Huang ZP, Ding J, Yan J, Hu X and Wang DZ: Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. Circ Res. 114:1585–1595. 2014. View Article : Google Scholar : PubMed/NCBI
39	Wang J, Yu F, Jia X, Iwanowycz S, Wang Y, Huang S, Ai W and Fan D: MicroRNA-155 deficiency enhances the recruitment and functions of myeloid-derived suppressor cells in tumor microenvironment and promotes solid tumor growth. Int J Cancer. 136:E602–E613. 2015. View Article : Google Scholar : PubMed/NCBI
40	Wan YC, Li T, Han YD, Zhang HY, Lin H and Zhang B: MicroRNA-155 enhances the activation of Wnt/β-catenin signaling in colorectal carcinoma by suppressing HMG-box transcription factor 1. Mol Med Rep. 13:2221–2228. 2016. View Article : Google Scholar : PubMed/NCBI
41	Tu YX, Wang SB, Fu LQ, Li SS, Guo QP, Wu Y, Mou XZ and Tong XM: Ovatodiolide targets chronic myeloid leukemia stem cells by epigenetically upregulating hsa-miR-155, suppressing the BCR-ABL fusion gene and dysregulating the PI3K/AKT/mTOR pathway. Oncotarget. 9:3267–3277. 2017. View Article : Google Scholar : PubMed/NCBI
42	Zhang L, Wang W, Li X, He S, Yao J, Wang X, Zhang D and Sun X: MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2. Int J Oncol. 48:2425–2434. 2016. View Article : Google Scholar : PubMed/NCBI
43	Liu D, Han P, Gao C, Gao W, Yao X and Liu S: microRNA-155 modulates hepatic stellate cell proliferation, apoptosis, and cell cycle progression in rats with alcoholic hepatitis via the MAPK signaling pathway through targeting SOCS1. Front Pharmacol. 11:2702020. View Article : Google Scholar : PubMed/NCBI
44	Chen L, Ming X, Li W, Bi M, Yan B, Wang X, Yang P and Yang B: The microRNA-155 mediates hepatitis B virus replication by reinforcing SOCS1 signalling-induced autophagy. Cell Biochem Funct. 38:436–442. 2020. View Article : Google Scholar : PubMed/NCBI
45	Ye J, Guo R, Shi Y, Qi F, Guo C and Yang L: miR-155 regulated inflammation response by the SOCS1-STAT3-PDCD4 axis in Atherogenesis. Mediators Inflamm. 2016:80601822016. View Article : Google Scholar : PubMed/NCBI
46	Yang Y, Yang L, Liang X and Zhu G: MicroRNA-155 promotes atherosclerosis inflammation via targeting SOCS1. Cell Physiol Biochem. 36:1371–1381. 2015. View Article : Google Scholar : PubMed/NCBI
47	Bouamar H, Jiang D, Wang L, Lin AP, Ortega M and Aguiar RC: MicroRNA 155 control of p53 activity is context dependent and mediated by Aicda and Socs1. Mol Cell Biol. 35:1329–1340. 2015. View Article : Google Scholar : PubMed/NCBI