Home LiteratureArticle Details
PMID: 20353950 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15S-hydroxyeicosatetraenoic acid-induced angiogenesis.

The Journal of biological chemistry ·Vol. 285 ·No. 22 ·2010-05-28 ·Pages 16830-43

Singh NK, Quyen DV, Kundumani-Sridharan V, Brooks PC, Rao GN

Abstract

To understand the involvement of matrix metalloproteinases (MMPs) in 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)-induced angiogenesis, we have studied the role of MMP-2. 15(S)-HETE induced MMP-2 expression and activity in a time-dependent manner in human dermal microvascular endothelial cells (HDMVECs). Inhibition of MMP-2 activity or depletion of its levels attenuated 15(S)-HETE-induced HDMVEC migration, tube formation, and Matrigel plug angiogenesis. 15(S)-HETE also induced Fra-1 and c-Jun expression in a Rac1-MEK1-JNK1-dependent manner. In addition, 15(S)-HETE-induced MMP-2 expression and activity were mediated by Rac1-MEK1-JNK1-dependent activation of AP-1 (Fra-1/c-Jun). Cloning and site-directed mutagenesis of MMP-2 promoter revealed that AP-1 site proximal to the transcriptional start site is required for 15(S)-HETE-induced MMP-2 expression, and Fra-1 and c-Jun are the essential components of AP-1 that bind to MMP-2 promoter in response to 15(S)-HETE. Hind limb ischemia led to an increase in MEK1 and JNK1 activation and Fra-1, c-Jun, and MMP-2 expression resulting in enhanced neovascularization and recovery of blood perfusion in wild-type mice as compared with 12/15-Lox(-/-) mice. Together, these results provide the first direct evidence for a role of 12/15-Lox-12/15(S)-HETE axis in the regulation of ischemia-induced angiogenesis.

MeSH Terms
Animals Base Sequence Cell Movement Gene Expression Regulation, Enzymologic Humans Hydroxyeicosatetraenoic Acids/metabolism Ischemia Matrix Metalloproteinase 2/metabolism Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Neovascularization, Pathologic Promoter Regions, Genetic Proto-Oncogene Proteins c-fos/metabolism Transcription Factor AP-1/physiology
Chemicals
Hydroxyeicosatetraenoic Acids Proto-Oncogene Proteins c-fos Transcription Factor AP-1 fos-related antigen 1 15-hydroxy-5,8,11,13-eicosatetraenoic acid Matrix Metalloproteinase 2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Singh Nikhlesh K
Department of Physiology, the University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Quyen Dong Van
Kundumani-Sridharan Venkatesh
Brooks Peter C
Rao Gadiparthi N
References (68)
68 references, click to expand
  1. Spatial and temporal expression of the 72-kDa type IV collagenase (MMP-2) correlates with development and differentiation of valves in the embryonic avian heart.
    Dev Dyn. 1997 Jul;209(3):261-8 PMID: 9215641
  2. 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Src-mediated Egr-1-dependent rapid induction of FGF-2 expression.
    Blood. 2010 Mar 11;115(10):2105-16 PMID: 20053757
  3. Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9.
    J Biol Chem. 2003 May 16;278(20):18140-5 PMID: 12642591
  4. The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression.
    Methods Mol Biol. 2001;151:121-48 PMID: 11217296
  5. Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve.
    Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10999-1004 PMID: 16043715
  6. Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester.
    Biochem J. 1993 Dec 15;296 ( Pt 3):803-9 PMID: 8280080
  7. Chronic hypoxia activates lung 15-lipoxygenase, which catalyzes production of 15-HETE and enhances constriction in neonatal rabbit pulmonary arteries.
    Circ Res. 2003 May 16;92(9):992-1000 PMID: 12690037
  8. Src-dependent STAT-3-mediated expression of monocyte chemoattractant protein-1 is required for 15(S)-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration.
    J Biol Chem. 2009 Nov 6;284(45):31142-55 PMID: 19736311
  9. Molecular cloning and primary structure of human 15-lipoxygenase.
    Biochem Biophys Res Commun. 1988 Dec 15;157(2):457-64 PMID: 3202857
  10. The AP-1 site and MMP gene regulation: what is all the fuss about?
    Matrix Biol. 1997 Mar;15(8-9):519-26 PMID: 9138284
  11. Lipoxygenase pathways in atherogenesis.
    Trends Cardiovasc Med. 2004 Jul;14(5):191-5 PMID: 15261891
  12. A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers.
    Biochem J. 2003 Feb 1;369(Pt 3):485-96 PMID: 12371906
  13. Plasminogen activators and matrix metalloproteinases in angiogenesis.
    Enzyme Protein. 1996;49(1-3):117-37 PMID: 8797002
  14. Discovery of a second 15S-lipoxygenase in humans.
    Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6148-52 PMID: 9177185
  15. Matrix metalloproteinases and tumor metastasis.
    Cancer Metastasis Rev. 2006 Mar;25(1):9-34 PMID: 16680569
  16. c-Jun NH(2)-terminal kinase is essential for the regulation of AP-1 by tumor necrosis factor.
    Mol Cell Biol. 2003 Apr;23(8):2871-82 PMID: 12665585
  17. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells.
    EMBO J. 2003 May 15;22(10):2411-21 PMID: 12743035
  18. Rho GTPases in cell biology.
    Nature. 2002 Dec 12;420(6916):629-35 PMID: 12478284
  19. Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility.
    J Lipid Res. 2006 Apr;47(4):767-77 PMID: 16382163
  20. Temporal exposure of cryptic collagen epitopes within ischemic muscle during hindlimb reperfusion.
    Am J Pathol. 2005 Nov;167(5):1349-59 PMID: 16251419
  21. Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier.
    J Biol Chem. 2001 May 11;276(19):16248-56 PMID: 11340084
  22. Cardiac morphogenesis: matrix metalloproteinase coordination of cellular mechanisms underlying heart tube formation and directionality of looping.
    Dev Dyn. 2005 Jul;233(3):739-53 PMID: 15844197
  23. Matrix metalloproteinase-2-deficient fibroblasts exhibit an alteration in the fibrotic response to connective tissue growth factor/CCN2 because of an increase in the levels of endogenous fibronectin.
    J Biol Chem. 2009 May 15;284(20):13551-13561 PMID: 19276073
  24. 15-lipoxygenase-1 prevents vascular endothelial growth factor A- and placental growth factor-induced angiogenic effects in rabbit skeletal muscles via reduction in growth factor mRNA levels, NO bioactivity, and downregulation of VEGF receptor 2 expression.
    Circ Res. 2008 Feb 1;102(2):177-84 PMID: 17991885
  25. Statin treated patients have reduced intraplaque angiogenesis in carotid endarterectomy specimens.
    Atherosclerosis. 2007 Jun;192(2):457-63 PMID: 17335827
  26. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) as the predominant eicosanoid in aortas from Watanabe Heritable Hyperlipidemic and cholesterol-fed rabbits.
    Atherosclerosis. 1989 Jan;75(1):31-8 PMID: 2495011
  27. 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires STAT3-dependent expression of VEGF.
    Cancer Res. 2007 May 1;67(9):4328-36 PMID: 17483346
  28. Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice.
    J Clin Invest. 1999 Jun;103(11):1597-604 PMID: 10359569
  29. Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression.
    Blood. 2006 Sep 1;108(5):1441-50 PMID: 16609063
  30. Overexpression of 12/15-lipoxygenase, an ortholog of human 15-lipoxygenase-1, in the prostate tumors of TRAMP mice.
    Neoplasia. 2004 Nov-Dec;6(6):821-30 PMID: 15720809
  31. Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis.
    Dev Biol. 2008 Jan 1;313(1):196-209 PMID: 18022611
  32. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.
    Nat Med. 2006 Aug;12(8):939-44 PMID: 16862152
  33. Matrix metalloproteinases in cerebrovascular diseases.
    Cerebrovasc Dis. 2005;20(3):141-51 PMID: 16088108
  34. Cell migration: Rho GTPases lead the way.
    Dev Biol. 2004 Jan 1;265(1):23-32 PMID: 14697350
  35. Matrix metalloproteinase synthesis and expression in isolated LV myocyte preparations.
    Am J Physiol. 1999 Aug;277(2):H777-87 PMID: 10444506
  36. 15-Lipoxygenase-2 expression in benign and neoplastic lung: an immunohistochemical study and correlation with tumor grade and proliferation.
    Hum Pathol. 2004 Jul;35(7):840-9 PMID: 15257547
  37. Matrix metalloproteinases: regulation and dysregulation in the failing heart.
    Circ Res. 2002 Mar 22;90(5):520-30 PMID: 11909815
  38. Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1.
    J Biol Chem. 2009 Jun 26;284(26):17877-82 PMID: 19403949
  39. Angiogenesis in cancer, vascular, rheumatoid and other disease.
    Nat Med. 1995 Jan;1(1):27-31 PMID: 7584949
  40. Matrix metalloproteinases: effectors of development and normal physiology.
    Genes Dev. 2000 Sep 1;14(17):2123-33 PMID: 10970876
  41. Matrix metalloproteinases and cardiovascular disease.
    Circ Res. 1995 Nov;77(5):863-8 PMID: 7554139
  42. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.
    Circ Res. 2003 May 2;92(8):827-39 PMID: 12730128
  43. Collagenolytic activity in amphibian tissues: a tissue culture assay.
    Proc Natl Acad Sci U S A. 1962 Jun 15;48:1014-22 PMID: 13902219
  44. Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1.
    Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7069-74 PMID: 8692946
  45. 15(S)-HETE production in human retinal microvascular endothelial cells by hypoxia: Novel role for MEK1 in 15(S)-HETE induced angiogenesis.
    Invest Ophthalmol Vis Sci. 2007 Nov;48(11):4930-8 PMID: 17962441
  46. CREB-mediated IL-6 expression is required for 15(S)-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration.
    Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):809-15 PMID: 19342597
  47. Therapeutic angiogenesis for ischemic cardiovascular disease.
    J Mol Cell Cardiol. 2001 Mar;33(3):379-93 PMID: 11181008
  48. 15(S)-hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K-Akt-mTOR-S6K1 signaling.
    Cancer Res. 2005 Aug 15;65(16):7283-91 PMID: 16103079
  49. Angiogenesis-dependent and independent phases of intimal hyperplasia.
    Circulation. 2004 Oct 19;110(16):2436-43 PMID: 15477408
  50. E-cadherin engagement stimulates proliferation via Rac1.
    J Cell Biol. 2006 May 8;173(3):431-41 PMID: 16682529
  51. A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis.
    J Lipid Res. 2009 Mar;50(3):521-533 PMID: 18849464
  52. Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter.
    Mol Cell Biol. 1997 Nov;17(11):6330-8 PMID: 9343394
  53. 15-HETE suppresses K(+) channel activity and inhibits apoptosis in pulmonary artery smooth muscle cells.
    Apoptosis. 2009 Jan;14(1):42-51 PMID: 19082729
  54. The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B-dependent expression of interleukin-8.
    Blood. 2009 Jun 4;113(23):6023-33 PMID: 19349617
  55. Activation of MMP-2 in response to vascular injury is mediated by phosphatidylinositol 3-kinase-dependent expression of MT1-MMP.
    Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2861-70 PMID: 15297252
  56. Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure?
    Circ Res. 2001 Aug 3;89(3):201-10 PMID: 11485970
  57. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly.
    Circ Res. 2002 Feb 22;90(3):251-62 PMID: 11861412
  58. Role of 12-lipoxygenase in hypoxia-induced rat pulmonary artery smooth muscle cell proliferation.
    Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L367-74 PMID: 16199435
  59. Cross talk between cell-cell and cell-matrix adhesion signaling pathways during heart organogenesis: implications for cardiac birth defects.
    Microsc Microanal. 2005 Jun;11(3):200-8 PMID: 16060972
  60. Metalloproteinases, inflammation, and rheumatoid arthritis.
    Ann Rheum Dis. 2003 Nov;62 Suppl 2:ii43-7 PMID: 14532148
  61. Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family.
    J Biol Chem. 1996 Nov 1;271(44):27225-8 PMID: 8910292
  62. Signal transduction by the JNK group of MAP kinases.
    Cell. 2000 Oct 13;103(2):239-52 PMID: 11057897
  63. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs.
    Cell. 1995 Jun 30;81(7):1147-57 PMID: 7600582
  64. Formation of 15-HETE as a major hydroxyeicosatetraenoic acid in the atherosclerotic vessel wall.
    Biochim Biophys Acta. 1985 Apr 25;834(2):272-4 PMID: 3995065
  65. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion.
    Circ Res. 1994 Jul;75(1):181-9 PMID: 8013077
  66. Ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevents intimal hyperplasia in balloon-injured rat carotid arteries.
    Circulation. 2001 Mar 13;103(10):1446-52 PMID: 11245651
  67. Making the cut: protease-mediated regulation of angiogenesis.
    Exp Cell Res. 2006 Mar 10;312(5):608-22 PMID: 16442099
  68. Dual 12/15- and 5-lipoxygenase deficiency in macrophages alters arachidonic acid metabolism and attenuates peritonitis and atherosclerosis in ApoE knock-out mice.
    J Biol Chem. 2009 Jul 31;284(31):21077-89 PMID: 19509298
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M110.106187
Published
2010-05-28
Epub
2010-00-29
Pages
16830-43
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2878006
Subset
IM
Grants
NCI NIH HHS · R01 CA091645 · United States
NHLBI NIH HHS · R01 HL074860 · United States
NHLBI NIH HHS · HL074860 · United States
External Links
PubMed source DOI: 10.1074/jbc.M110.106187 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2