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Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways

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Abstract

Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces a dose- and time-dependent increase in MMP-2 expression in rat vascular smooth muscle cells (VSMC). Treatment with either the Rho-associated protein kinase (ROCK) inhibitor Y-27632 or suppression of ROCK-1/2 by small interfering RNA technology significantly reduced the MMP-2 expression, thus suggesting that ROCK regulates such expression. Similar results were observed when VSMC were pretreated with either U0126 or SB203580, which are selective inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, respectively, thus suggesting that these kinases are important for the induction of MMP-2 expression by PDGF-BB. In conclusion, these results described a novel mechanism in atherosclerosis through PDGF-BB signaling in VSMC, in which MMP-2 expression is induced via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase phosphorylation, as well as ROCK.

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Abbreviations

VSMC:

Vascular smooth muscle cells

PDGF-BB:

Platelet-derived growth factor-BB

ROCK:

Rho-associated protein kinase

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinases

ERK:

Extracellular signal-regulated kinase

SDS:

Sodium dodecyl sulfate

PVDF:

Polyvinylidene difluoride

TBS:

Tris-buffered saline

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

References

  1. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809

    Article  CAS  PubMed  Google Scholar 

  2. Willis A, Pierre-Paul D, Sumpio B, Gahtan V (2004) Vascular smooth muscle cell migration: current research and clinical implications. Vasc Endovasc Surg 38:11–23

    Article  CAS  Google Scholar 

  3. Ferns G, Raines EW, Sprugel KH, Motani AS, Reidy MA, Ross R (1991) Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 253:1129–1132

    Article  CAS  PubMed  Google Scholar 

  4. Claesson-Welsh L (1994) Platelet-derived growth factor receptor signals. J Biol Chem 269:32023–32026

    CAS  PubMed  Google Scholar 

  5. Akiyama N, Naruse K, Kobayashi Y, Nakamura N, Hamada Y, Nakashima E, Matsubara T, Oiso Y, Nakamura J (2008) High glucose-induced upregulation of Rho/Rho-kinase via platelet-derived growth factor receptor-β increases migration of aortic smooth muscle cells. J Mol Cell Cardiol 45:326–332

    Article  CAS  PubMed  Google Scholar 

  6. Ishikura K, Fujita H, Hida M, Awazu M (2005) Trapidil inhibits platelet-derived growth factor-induced migration via protein kinase A and RhoA/Rho-associated kinase in rat vascular smooth muscle cells. Eur J Pharmacol 515:28–33

    Article  CAS  PubMed  Google Scholar 

  7. Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9:267–285

    Article  CAS  PubMed  Google Scholar 

  8. Newby AC (2006) Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 69:614–624

    Article  CAS  PubMed  Google Scholar 

  9. Sasaguri Y, Murahashi N, Kato S, Hiraoka K, Morimatsu M (1994) Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells. Atherosclerosis 109:94

    Article  Google Scholar 

  10. Nanni S, Melandri G, Hanemaaijer R, Cervi V, Tomasi L, Altimari A, Van Lent N, Tricoci P, Bacchi L, Branzi A (2007) Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms. Transl Res 149:137–144

    Article  CAS  PubMed  Google Scholar 

  11. Wang M, Takagi G, Asai K, Resuello RG, Natividad FF, Vatner DE, Vatner SF, Lakatta EG (2003) Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates. Hypertension 41:1308–1316

    Article  CAS  PubMed  Google Scholar 

  12. Luchtefeld M, Grote K, Grothusen C, Bley S, Bandlow N, Selle T, Strüber M, Haverich A, Bavendiek U, Drexler H (2005) Angiotensin II induces MMP-2 in a p47phox-dependent manner. Biochem Biophys Res Commun 328:183–188

    Article  CAS  PubMed  Google Scholar 

  13. Deatrick KB, Luke CE, Elfline MA, Sood V, Baldwin J, Upchurch GR Jr, Jaffer FA, Wakefield TW, Henke PK (2013) The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling. J Vasc Surg 58:1375–1384

    Article  PubMed  Google Scholar 

  14. Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK (2009) ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res 104:531–540

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Zhao Y, Lv M, Lin H, Cui Y, Wei X, Qin Y, Kohama K, Gao Y (2013) Rho-associated protein kinase isoforms stimulate proliferation of vascular smooth muscle cells through ERK and induction of cyclin D1 and PCNA. Biochem Biophys Res Commun 432:488–493

    Article  CAS  PubMed  Google Scholar 

  16. Marinissen MJ, Chiariello M, Tanos T, Bernard O, Narumiya S, Gutkind JS (2004) The small GTP-binding protein RhoA regulates c-jun by a ROCK-JNK signaling axis. Mol Cell 14:29–41

    Article  CAS  PubMed  Google Scholar 

  17. Appleton CTG, Usmani SE, Mort JS, Beier F (2009) Rho/ROCK and MEK/ERK activation by transforming growth factor-α induces articular cartilage degradation. Lab Invest 90:20–30

    Article  PubMed  Google Scholar 

  18. Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869

    CAS  PubMed  Google Scholar 

  19. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331

    Article  CAS  PubMed  Google Scholar 

  20. Zhan Y, Kim S, Izumi Y, Izumiya Y, Nakao T, Miyazaki H, Iwao H (2003) 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

    Article  CAS  PubMed  Google Scholar 

  21. Zhao Y, Lv M, Lin H, Hong Y, Yang F, Sun Y, Guo Y, Cui Y, Li S, Gao Y (2012) ROCK1 induces ERK nuclear translocation in PDGF-BB-stimulated migration of rat vascular smooth muscle cells. IUBMB Life 64:194–202

    Article  CAS  PubMed  Google Scholar 

  22. Li S, Tanaka H, Wang HH, Yoshiyama S, Kumagai H, Nakamura A, Brown DL, Thatcher SE, Wright GL, Kohama K (2006) Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation. Am J Physiol Heart Circ Physiol 291:H1262–H1272

    Article  CAS  PubMed  Google Scholar 

  23. Jung HO, Uhm JS, Seo SM, Kim JH, Youn H-J, Baek SH, Chung WS, Seung KB (2010) Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression. Biochem Biophys Res Commun 402:577–582

    Article  CAS  PubMed  Google Scholar 

  24. Jiménez E, de la Blanca EP, Urso L, González I, Salas J, Montiel M (2009) Angiotensin II induces MMP 2 activity via FAK/JNK pathway in human endothelial cells. Biochem Biophys Res Commun 380:769–774

    Article  PubMed  Google Scholar 

  25. Bendeck MP, Conte M, Zhang M, Nili N, Strauss BH, Farwell SM (2002) Doxycycline modulates smooth muscle cell growth, migration, and matrix remodeling after arterial injury. Am J Pathol 160:1089–1095

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Wang Y, Hu C, Dong R, Huang X, Qiu H (2011) Platelet-derived growth factor-D promotes ovarian cancer invasion by regulating matrix metalloproteinases 2 and 9. Asian Pac J Cancer Prev 12:3367–3370

    PubMed  Google Scholar 

  27. Qin Y, Fan F, Zhao Y, Cui Y, Wei X, Kohama K, Gordon JR, Li F, Gao Y (2013) Recombinant human CXCL8 (3–72) K11R/G31P regulates smooth muscle cell proliferation and migration through blockage of interleukin-8 receptor. IUBMB Life 65:67–75

    Article  CAS  PubMed  Google Scholar 

  28. Genersch E, Hayess K, Neuenfeld Y, Haller H (2000) Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and-independent pathways. J Cell Sci 113:4319–4330

    CAS  PubMed  Google Scholar 

  29. Zaragoza C, Soria E, López E, Browning D, Balbín M, López-Otín C, Lamas S (2002) Activation of the mitogen activated protein kinase extracellular signal-regulated kinase 1 and 2 by the nitric oxide–cGMP–cGMP-dependent protein kinase axis regulates the expression of matrix metalloproteinase 13 in vascular endothelial cells. Mol Pharmacol 62:927–935

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 31070719 and No. 31370800).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Lvshun, Dalian, 116044, People’s Republic of China

    Ying Cui, Yin-Wei Sun, Hai-Shuang Lin, Wei-Min Su, Yan Fang, Yuan-Hua Qin & Ying Gao

  2. Provincial Key Laboratory of Cell and Molecular Biology, Dalian Medical University, Lvshun, Dalian, 116044, People’s Republic of China

    Ying Zhao, Xiao-Qing Wei & Ying Gao

  3. Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo, Tokyo, 202-8585, Japan

    Kazuhiro Kohama

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  1. Ying Cui
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Correspondence to Ying Gao.

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Cui, Y., Sun, YW., Lin, HS. et al. Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways. Mol Cell Biochem 393, 255–263 (2014). https://doi.org/10.1007/s11010-014-2068-5

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  • DOI: https://doi.org/10.1007/s11010-014-2068-5

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