Open Access

COL6A1 knockdown suppresses cell proliferation and migration in human aortic vascular smooth muscle cells

  • Authors:
    • Zongxiang Chen
    • Qingjian Wu
    • Chengjun Yan
    • Juan Du
  • View Affiliations

  • Published online on: July 19, 2019     https://doi.org/10.3892/etm.2019.7798
  • Pages: 1977-1984
  • Copyright: © Chen 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: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Vascular smooth muscle cell (VSMC) migration is an important pathophysiological signature of neointimal hyperplasia. The aim of the present study was to investigate the effects of collagen type VI α1 chain (COL6A1) on VSMC migration. COL6A1 expression was silenced in platelet‑derived growth factor (PDGF‑BB)‑stimulated VSMCs. Cell counting kit‑8, wound healing and Transwell assays were used to measure cell viability, migration and invasion, respectively. Reverse transcription‑quantitative PCR and western blot analysis were performed to analyze the expression of factors associated with metastasis. COL6A1 silencing attenuated PDGF‑BB‑induced increases in cell viability and invasive abilities of VSMCs, in addition to partially reversing the increased expression of fibronectin (FN), matrix metalloproteinase (MMP)‑2 and MMP‑9 induced by PDGF‑BB stimulation. The silencing of COL6A also overturned PDGF‑BB‑induced reduction in tissue inhibitor of metalloproteinase 2 expression in VSMCs. PDGF‑BB activated the AKT/mTOR pathway, which was also inhibited by COL6A1 knockdown. Taken together, these findings suggest that COL6A1 silencing inhibited VSMC viability and migration by inhibiting AKT/mTOR activation.

References

1 

Tian Y, Deng P, Li B, Wang J, Li J, Huang Y and Zheng Y: Treatment models of cardiac rehabilitation in patients with coronary heart disease and related factors affecting patient compliance. Rev Cardiovasc Med. 20:27–33. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Khamis RY, Ammari T and Mikhail GW: Gender differences in coronary heart disease. Heart. 102:1142–1149. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Orme RC, Parker WAE, Thomas MR, Judge HM, Baster K, Sumaya W, Morgan KP, McMellon HC, Richardson JD, Grech ED, et al: Study of two dose regimens of ticagrelor compared with clopidogrel in patients undergoing percutaneous coronary intervention for stable coronary artery disease (STEEL-PCI). Circulation. Jun 21–2018.(Epub ahead of print) doi: 10.1161/CIRCULATIONAHA.118.034790. View Article : Google Scholar : PubMed/NCBI

4 

Lee MS, Cheng RK, Kandzari DE and Kirtane AJ: Long-term outcomes of heart transplantation recipients with transplant coronary artery disease who develop in-stent restenosis after percutaneous coronary intervention. Am J Cardiol. 109:1729–1732. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Prasad K: Do statins have a role in reduction/prevention of post-PCI restenosis? Cardiovasc Ther. 31:12–26. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Fang CY, Fang HY, Chen CJ, Yang CH, Wu CJ and Lee WC: Comparison of clinical outcomes after drug-eluting balloon and drug-eluting stent use for in-stent restenosis related acute myocardial infarction: A retrospective study. PeerJ. 6:e46462018. View Article : Google Scholar : PubMed/NCBI

7 

Lee KJ, Park SH, Lee JY, Joo HC, Jang EH, Youn YN and Ryu W: Perivascular biodegradable microneedle cuff for reduction of neointima formation after vascular injury. J Control Release. 192:174–181. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Ishimura S, Furuhashi M, Mita T, Fuseya T, Watanabe Y, Hoshina K, Kokubu N, Inoue K, Yoshida H and Miura T: Reduction of endoplasmic reticulum stress inhibits neointima formation after vascular injury. Sci Rep. 4:69432014. View Article : Google Scholar : PubMed/NCBI

9 

Guan H, Gao L, Zhu L, Yan L, Fu M, Chen C, Dong X, Wang L, Huang K and Jiang H: Apigenin attenuates neointima formation via suppression of vascular smooth muscle cell phenotypic transformation. J Cell Biochem. 113:1198–1207. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Zhang J, Chen J, Xu C, Yang J, Guo Q, Hu Q and Jiang H: Resveratrol inhibits phenotypic switching of neointimal vascular smooth muscle cells after balloon injury through blockade of Notch pathway. J Cardiovasc Pharmacol. 63:233–239. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Tang L, Dai F, Liu Y, Yu X, Huang C, Wang Y and Yao W: RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton. Pharmacol Res. 133:201–212. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Yang F, Chen Q, He S, Yang M, Maguire EM, An W, Afzal TA, Luong LA, Zhang L and Xiao Q: miR-22 is a novel mediator of vascular smooth muscle cell phenotypic modulation and neointima formation. Circulation. 137:1824–1841. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Hasanov Z, Ruckdeschel T, König C, Mogler C, Kapel SS, Korn C, Spegg C, Eichwald V, Wieland M, Appak S and Augustin HG: Endosialin promotes atherosclerosis through phenotypic remodeling of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 37:495–505. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Shi N, Li CX, Cui XB, Tomarev SI and Chen SY: Olfactomedin 2 regulates smooth muscle phenotypic modulation and vascular remodeling through mediating runt-related transcription factor 2 binding to serum response factor. Arterioscler Thromb Vasc Biol. 37:446–454. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Wang JC, Li GY, Wang B, Han SX, Sun X, Jiang YN, Shen YW, Zhou C, Feng J, Lu SY, et al: Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation. J Exp Clin Cancer Res. 38:2352019. View Article : Google Scholar : PubMed/NCBI

16 

Hellström M, Kalén M, Lindahl P, Abramsson A and Betsholtz C: Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 126:3047–3055. 1999.PubMed/NCBI

17 

Zhan Y, Kim S, Izumi Y, Izumiya Y, Nakao T, Miyazaki H and Iwao H: Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression. Arterioscler Thromb Vasc Biol. 23:795–801. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Satoh K, Kikuchi N, Kurosawa R and Shimokawa H: PDE1C negatively regulates growth factor receptor degradation and promotes VSMC proliferation. Circ Res. 116:1098–1100. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Hou T, Tong C, Kazobinka G, Zhang W, Huang X, Huang Y and Zhang Y: Expression of COL6A1 predicts prognosis in cervical cancer patients. Am J Transl Res. 8:2838–2844. 2016.PubMed/NCBI

20 

Wan F, Wang H, Shen Y, Zhang H, Shi G, Zhu Y, Dai B and Ye D: Upregulation of COL6A1 is predictive of poor prognosis in clear cell renal cell carcinoma patients. Oncotarget. 6:27378–27387. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Nandakumar P, Lee D, Richard MA, Tekola-Ayele F, Tayo BO, Ware E, Sung YJ, Salako B, Ogunniyi A, Gu CC, et al: Rare coding variants associated with blood pressure variation in 15 914 individuals of African ancestry. J Hypertens. 35:1381–1389. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Sleptsov AA, Nazarenko MS, Lebedev IN, Skriabin NA, Frolov AV, Popov VA, Barbarash LS and Puzyrev VP: Somatic genome variations in vascular tissues and peripheral blood leukocytes in patients with atherosclerosis. Genetika. 50:986–995. 2014.(In Russian). PubMed/NCBI

23 

Chiu KH, Chang YH, Wu YS, Lee SH and Liao PC: Quantitative secretome analysis reveals that COL6A1 is a metastasis-associated protein using stacking gel-aided purification combined with iTRAQ labeling. J Proteome Res. 10:1110–1125. 2011. View Article : Google Scholar : PubMed/NCBI

24 

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

25 

Zhang MJ, Zhou Y, Chen L, Wang YQ, Wang X, Pi Y, Gao CY, Li JC and Zhang LL: An overview of potential molecular mechanisms involved in VSMC phenotypic modulation. Histochem Cell Biol. 145:119–130. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Fellows BD, Ghobrial N, Mappus E, Hargett A, Bolding M, Dean D and Mefford OT: In vitro studies of heparin-coated magnetic nanoparticles for use in the treatment of neointimal hyperplasia. Nanomedicine. 14:1191–1200. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Chen S, Liu B, Kong D, Li S, Li C, Wang H and Sun Y: Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway. PLoS One. 10:e01225772015. View Article : Google Scholar : PubMed/NCBI

28 

Sato T, Takano R, Tokunaka K, Saiga K, Tomura A, Sugihara H, Hayashi T, Imamura Y and Morita M: Type VI collagen α1 chain polypeptide in non-triple helical form is an alternative gene product of COL6A1. J Biochem. 164:173–181. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Prado AF, Pernomian L, Azevedo A, Costa RAP, Rizzi E, Ramos J, Paes Leme AF, Bendhack LM, Tanus-Santos JE and Gerlach RF: Matrix metalloproteinase-2-induced epidermal growth factor receptor transactivation impairs redox balance in vascular smooth muscle cells and facilitates vascular contraction. Redox Biol. 18:181–190. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Ou YC, Li JR, Wang JD, Chang CY, Wu CC, Chen WY, Kuan YH, Liao SL, Lu HC and Chen CJ: Fibronectin promotes cell growth and migration in human renal cell carcinoma cells. Int J Mol Sci. 20:E27922019. View Article : Google Scholar : PubMed/NCBI

31 

Dhar S, Sun Z, Meininger GA and Hill MA: Nonenzymatic glycation interferes with fibronectin-integrin interactions in vascular smooth muscle cells. Microcirculation. 24:2017.doi: 10.1111/micc.12347. View Article : Google Scholar : PubMed/NCBI

32 

Hunter MC, O'Hagan KL, Kenyon A, Dhanani KC, Prinsloo E and Edkins AL: Hsp90 binds directly to fibronectin (FN) and inhibition reduces the extracellular fibronectin matrix in breast cancer cells. PLoS One. 9:e868422014. View Article : Google Scholar : PubMed/NCBI

33 

Yang M, Fan Z, Wang F, Tian ZH, Ma B, Dong B, Li Z, Zhang M and Zhao W: BMP-2 enhances the migration and proliferation of hypoxia-induced VSMCs via actin cytoskeleton, CD44 and matrix metalloproteinase linkage. Exp Cell Res. 368:248–257. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Yin J, Xia W, Wu M, Zhang Y, Huang S, Zhang A and Jia Z: Inhibition of mitochondrial complex I activity attenuates neointimal hyperplasia by inhibiting smooth muscle cell proliferation and migration. Chem Biol Interact. 304:73–82. 2019. View Article : Google Scholar : PubMed/NCBI

35 

Song IS, Jeong YJ, Park JH, Shim S and Jang SW: Chebulinic acid inhibits smooth muscle cell migration by suppressing PDGF-Rβ phosphorylation and inhibiting matrix metalloproteinase-2 expression. Sci Rep. 7:117972017. View Article : Google Scholar : PubMed/NCBI

36 

Seo KW, Lee SJ, Ye BH, Kim YW, Bae SS and Kim CD: Mechanical stretch enhances the expression and activity of osteopontin and MMP-2 via the Akt1/AP-1 pathways in VSMC. J Mol Cell Cardiol. 85:13–24. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Smiljanic K, Obradovic M, Jovanovic A, Djordjevic J, Dobutovic B, Jevremovic D, Marche P and Isenovic ER: Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: Involvement of MMP-2. Mol Cell Biochem. 396:147–160. 2014. View Article : Google Scholar : PubMed/NCBI

38 

Hu Q, Lin X, Ding L, Zeng Y, Pang D, Ouyang N, Xiang Y and Yao H: ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma. Cancer Med. 7:3862–3874. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Han R, Gu S, Zhang Y, Luo A, Jing X, Zhao L, Zhao X and Zhang L: Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-kappaB signaling. Sci Rep. 8:95752018. View Article : Google Scholar : PubMed/NCBI

40 

Zhou H, Wu Q, Wei L and Peng S: Paeoniflorin inhibits PDGFBBinduced human airway smooth muscle cell growth and migration. Mol Med Rep. 17:2660–2664. 2018.PubMed/NCBI

41 

Chan CM, Chang HH, Wang VC, Huang CL and Hung CF: Inhibitory effects of resveratrol on PDGF-BB-induced retinal pigment epithelial cell migration via PDGFRβ, PI3K/Akt and MAPK pathways. PLoS One. 8:e568192013. View Article : Google Scholar : PubMed/NCBI

42 

Wang H, Yin Y, Li W, Zhao X, Yu Y, Zhu J, Qin Z, Wang Q, Wang K, Lu W, et al: Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway. PLoS One. 7:e305032012. View Article : Google Scholar : PubMed/NCBI

43 

Cidad P, Miguel-Velado E, Ruiz-McDavitt C, Alonso E, Jiménez-Pérez L, Asuaje A, Carmona Y, García-Arribas D, López J, Marroquín Y, et al: Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway. Pflugers Arch. 467:1711–1722. 2015. View Article : Google Scholar : PubMed/NCBI

44 

Lu QB, Wan MY, Wang PY, Zhang CX, Xu DY, Liao X and Sun HJ: Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade. Redox Biol. 14:656–668. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Pan S, Lin H, Luo H, Gao F, Meng L, Zhou C, Jiang C, Guo Y, Ji Z, Chi J and Guo H: Folic acid inhibits dedifferentiation of PDGF-BB-induced vascular smooth muscle cells by suppressing mTOR/P70S6K signaling. Am J Transl Res. 9:1307–1316. 2017.PubMed/NCBI

Related Articles

Journal Cover

September 2019
Volume 18 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Chen, Z., Wu, Q., Yan, C., & Du, J. (2019). COL6A1 knockdown suppresses cell proliferation and migration in human aortic vascular smooth muscle cells. Experimental and Therapeutic Medicine, 18, 1977-1984. https://doi.org/10.3892/etm.2019.7798
MLA
Chen, Z., Wu, Q., Yan, C., Du, J."COL6A1 knockdown suppresses cell proliferation and migration in human aortic vascular smooth muscle cells". Experimental and Therapeutic Medicine 18.3 (2019): 1977-1984.
Chicago
Chen, Z., Wu, Q., Yan, C., Du, J."COL6A1 knockdown suppresses cell proliferation and migration in human aortic vascular smooth muscle cells". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1977-1984. https://doi.org/10.3892/etm.2019.7798