CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy

International Journal of Molecular Medicine

Volumn 36, Issue 6, 2015, Pages 1507-1518

  Di, Yu ^a   Zhang, Yiou ^a   Nie, Qingzhu ^a   Chen, Xiaolong ^a  

^a CHINA MEDICAL UNIVERSITY   (China)

Author keywords

Cysteine rich 61; Human umbilical vein endothelial cells; Phosphatidylinositol 3 kinase; Protein kinase B AKT; Retinal neovascularization; Retinopathy of prematurity

Indexed keywords

ADENOSINE DIPHOSPHATE; CYSTEINE RICH PROTEIN 61; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMALL INTERFERING RNA; 2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE; CHROMONE DERIVATIVE; MORPHOLINE DERIVATIVE; OXYGEN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NEWBORN; NONHUMAN; OXYGEN-INDUCED RETINOPATHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RETINA NEOVASCULARIZATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; UMBILICAL VEIN ENDOTHELIAL CELL; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL CULTURE; CELL HYPOXIA; CONFOCAL MICROSCOPY; DRUG EFFECTS; GENETICS; METABOLISM; RETROLENTAL FIBROPLASIA; RNA INTERFERENCE;

ANIMALS; ANIMALS, NEWBORN; APOPTOSIS; BLOTTING, WESTERN; CELL HYPOXIA; CELL PROLIFERATION; CELLS, CULTURED; CHROMONES; CYSTEINE-RICH PROTEIN 61; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; MALE; MICE, INBRED C57BL; MICROSCOPY, CONFOCAL; MORPHOLINES; OXYGEN; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RETINAL NEOVASCULARIZATION; RETINOPATHY OF PREMATURITY; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SIGNAL TRANSDUCTION;

EID: 84945337117     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2015.2371     Document Type: Article

References (66)

1. Li Z, He T, Du K, Xing YQ, Yan Y, Chen Z, Zhang H, and Shen Y. Overexpression of 15-lipoxygenase-1 in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via downregu-lation of vascular endothelial growth factor-A expression. Mol Vis 18: 2847-2859, 2012
2. Nowak-Sliwinska P, Storto M, Cataudella T, Ballini JP, Gatz R, Giorgio M, van Den Bergh H, Plyte S, and Wagnières G. Angiogenesis inhibition by the maleimide-based small molecule GNX-686. Microvasc Res 83: 105-110, 2012
3. Gergely K, and Gerinec A. Retinopathy of prematurity - epidemics, incidence, prevalence, blindness. Bratisl Lek Listy 111: 514-517, 2010
4. Wang F, Bai Y, Yu W, Han N, Huang L, Zhao M, Zhou A, Zhao M, and Li X. Anti-angiogenic effect of KH902 on retinal neovascularization. Graefes Arch Clin Exp Ophthalmol 251: 2131-2139, 2013
5. Hartnett ME, and Penn JS. Mechanisms, and management of retinopathy of prematurity. N Engl J Med 367: 2515-2526, 2012
6. Phelps DL. Retinopathy of prematurity. Pediatr Rev 16: 50-56, 1995
7. No authors listed: Cryotherapy for Retinopathy of Prematurity Cooperative Group: Multicenter trial of cryotherapy for reti-nopathy of prematurity. 3 1/2-year outcome - structure, and function. Arch Ophthalmol 111: 339-344, 1993
8. Xia XB, Xiong SQ, Song WT, Luo J, Wang YK, and Zhou RR. Inhibition of retinal neovascularization by siRNA targeting VEGF(165). Mol Vis 14: 1965-1973, 2008
9. Yan Y, He T, Shen Y, Chen X, Diao B, Li Z, Liu Q, and Xing YQ. Adenoviral 15-lipoxygenase-1 gene transfer inhibits hypoxia-induced proliferation of retinal microvascular endothelial cells in vitro. Int J Ophthalmol 5: 562-569, 2012
10. Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev 88: 937-941, 2012
11. Martínez-Castellanos MA, Schwartz S, Hernández-Rojas ML, Kon-Jara VA, García-Aguirre G, Guerrero-Naranjo JL, Chan RV, and Quiroz-Mercado H. Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up. Retina 33: 329-338, 2013
12. Hanna M, Liu H, Amir J, Sun Y, Morris SW, Siddiqui MA, Lau LF, and Chaqour B. Mechanical regulation of the proangiogenic factor CCN1/CYR61 gene requires the combined activities of MRTF-A, and CREB-binding protein histone acetyltransferase. J Biol Chem 284: 23125-23136, 2009
13. Jun JI, and Lau LF. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov 10: 945-963, 2011
14. Brigstock DR. The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Endocr Rev 20: 189-206, 1999
15. Brigstock DR. The CCN family: a new stimulus package. J Endocrinol 178: 169-175, 2003
16. Brigstock DR. Regulation of angiogenesis, and endothelial cell function by connective tissue growth factor (CTGF), and cysteine-rich 61 (CYR61). Angiogenesis 5: 153-165, 2002
17. Yan L, and Chaqour B. Cysteine-rich protein 61 (CCN1), and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular, and fibrovascular disease therapy. J Cell Commun Signal 7: 253-263, 2013
18. Choi J, Lin A, Shrier E, Lau LF, Grant MB, and Chaqour B. Degradome products of the matricellular protein CCN1 as modulators of pathological angiogenesis in the retina. J Biol Chem 288: 23075-23089, 2013
19. Chen CC, and Lau LF. Functions, and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 41: 771-783, 2009
20. Yang XM, Wang YS, Zhang J, Li Y, Xu JF, Zhu J, Zhao W, Chu DK, and Wiedemann P. Role of PI3K/Akt, and MEK/ERK in mediating hypoxia-induced expression of HIF-1alpha, and VEGF in laser-induced rat choroidal neovascularization. Invest Ophthalmol Vis Sci 50: 1873-1879, 2009
21. You JJ, Yang CH, Yang CM, and Chen MS. Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin α?β3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells. Cell Signal 26: 133-140, 2014
22. Sasore T, Reynolds AL, and Kennedy BN. Targeting the PI3K/Akt/mTOR pathway in ocular neovascularization. Adv Exp Med Biol 801: 805-811, 2014
23. Guo H, Lv Y, Tian T, Hu TH, Wang WJ, Sui X, Jiang L, Ruan ZP, and Nan KJ. Downregulation of p57 accelerates the growth, and invasion of hepatocellular carcinoma. Carcinogenesis 32: 1897 1904, 2011
24. Han Z, Yang Q, Liu B, Wu J, Li Y, Yang C, and Jiang Y. MicroRNA-622 functions as a tumor suppressor by targeting K-Ras, and enhancing the anticarcinogenic effect of resveratrol. Carcinogenesis 33: 131-139, 2012
25. Aubry JP, Blaecke A, Lecoanet-Henchoz S, Jeannin P, Herbault N, Caron G, Moine V, and Bonnefoy JY. Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry 37: 197-204, 1999
26. Vermes I, Haanen C, Steffens-Nakken H, and Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluo-rescein labelled Annexin V. J Immunol Methods 184: 39-51, 1995
27. Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, and D'Amore PA. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35: 101-111, 1994
28. Masuda I, Matsuo T, Yasuda T, and Matsuo N. Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci 37: 1914-1920, 1996
29. You JJ, Yang CH, Chen MS, and Yang CM. Cysteine-rich 61, a member of the CCN family, as a factor involved in the patho-genesis of proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 50: 3447-3455, 2009
30. Zhang Q, Zhang J, Guan Y, Zhang S, Zhu C, Xu GT, and Wang L. Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy. Graefes Arch Clin Exp Ophthalmol 247: 919-927, 2009
31. Hasan A, Pokeza N, Shaw L, Lee HS, Lazzaro D, Chintala H, Rosenbaum D, Grant MB, and Chaqour B. The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physi-ological adaptation of retinal vessels, and reduces pathological neovascularization associated with ischemic retinopathy. J Biol Chem 286: 9542-9554, 2011
32. Lambert V, Lecomte J, Hansen S, Blacher S, Gonzalez ML, Struman I, Sounni NE, Rozet E, de Tullio P, Foidart JM, et al. Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice. Nat Protoc 8: 2197-2211, 2013
33. Ecoiffier T, Yuen D, and Chen L. Differential distribution of blood, and lymphatic vessels in the murine cornea. Invest Ophthalmol Vis Sci 51: 2436-2440, 2010
34. Barnett JM, McCollum GW, Fowler JA, Duan JJ, Kay JD, Liu RQ, Bingaman DP, and Penn JS. Pharmacologic, and genetic manipu-lation of MMP-2, and -9 affects retinal neovascularization in rodent models of OIR. Invest Ophthalmol Vis Sci 48: 907-915, 2007
35. Park K, Chen Y, Hu Y, Mayo AS, Kompella UB, Longeras R, and Ma JX. Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization, and diabetes-induced retinal vascular leakage. Diabetes 58: 1902 1913, 2009
36. 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
37. Smith LE. Pathogenesis of retinopathy of prematurity. Acta Paediatr Suppl 91: 26-28, 2002
38. Grote K, Salguero G, Ballmaier M, Dangers M, Drexler H, and Schieffer B. The angiogenic factor CCN1 promotes adhesion, and migration of circulating CD34+ progenitor cells: potential role in angiogenesis, and endothelial regeneration. Blood 110: 877-885, 2007
39. Leu SJ, Lam SC, and Lau LF. Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3, and alpha6beta1 in human umbilical vein endothelial cells. J Biol Chem 277: 46248-46255, 2002
40. Kireeva ML, Latinkic BV, Kolesnikova TV, Chen CC, Yang GP, Abler AS, and Lau LF. Cyr61, and Fisp12 are both ECM-associated signaling molecules: Activities, metabolism, and localization during development. Exp Cell Res 233: 63-77, 1997
41. Kireeva ML, Mo FE, Yang GP, and Lau LF. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol 16: 1326 1334, 1996
42. Zhang X, Yu W, and Dong F. Cysteine-rich 61 (CYR61) is up-regulated in proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 250: 661-668, 2012
43. Meyuhas R, Pikarsky E, Tavor E, Klar A, Abramovitch R, Hochman J, Lago TG, and Honigman A. A Key role for cyclic AMP-responsive element binding protein in hypoxia-mediated activation of the angiogenesis factor CCN1 (CYR61) in Tumor cells. Mol Cancer Res 6: 1397-1409, 2008
44. Leask A. CCN1: A novel target for pancreatic cancer. J Cell Commun Signal 5: 123-124, 2011
45. Perbal B. CCN proteins: multifunctional signalling regulators. Lancet 363: 62-64, 2004
46. Su BC, and Mo FE. CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP. Cell Signal 26: 1326-1334, 2014
47. Gerszten RE, Friedrich EB, Matsui T, Hung RR, Li L, Force T, and Rosenzweig A. Role of phosphoinositide 3-kinase in monocyte recruitment under flow conditions. J Biol Chem 276: 26846-26851, 2001
48. Zheng ZZ, and Liu ZX. Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates CD151-induced endothelial cell proliferation, and cell migration. Int J Biochem Cell Biol 39: 340-348, 2007
49. Quan Y, Wang N, Chen Q, Xu J, Cheng W, Di M, Xia W, and Gao WQ SIRT3 inhibits prostate cancer by destabilizing onco-protein c-MYC through regulation of the PI3K/Aktpathway.Oncotarget 6 26494-26507 2015
50. Long QZ, Zhou M, Liu XG, Du YF, Fan JH, Li X, and He DL. Interaction of CCN1 with αvβ3 integrin induces P-glycoprotein, and confers vinblastine resistance in renal cell carcinoma cells. Anticancer Drugs 24: 810-817, 2013
51. Lin BR, Chang CC, Chen LR, Wu MH, Wang MY, Kuo IH, Chu CY, Chang KJ, Lee PH, Chen WJ, et al. Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1, and 2. Mol Cancer Res 5: 1111-1123, 2007
52. Lin MT, Kuo IH, Chang CC, Chu CY, Chen HY, Lin BR, Sureshbabu M, Shih HJ, and Kuo ML. Involvement of hypoxia-inducing factor-1alpha-dependent plasminogen activator inhibitor-1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem 283: 15807-15815, 2008
53. Hanrahan F, Humphries P, and Campbell M. RNAi-mediated barrier modulation: synergies of the brain, and eye. Ther Deliv 1: 587-594, 2010
54. Roy S, Nasser S, Yee M, Graves DT, and Roy S. A long-term siRNA strategy regulates fibronectin overexpression, and improves vascular lesions in retinas of diabetic rats. Mol Vis 17: 3166-3174, 2011
55. Kuwabara K, Ogawa S, Matsumoto M, Koga S, Clauss M, Pinsky DJ, Lyn P, Leavy J, Witte L, and Joseph-Silverstein J. Hypoxia-mediated induction of acidic/basic fibroblast growth factor, and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells. Proc Natl Acad Sci USA 92: 4606-4610, 1995
56. Kunz M, Hartmann A, Flory E, Toksoy A, Koczan D, Thiesen HJ, Mukaida N, Neumann M, Rapp UR, Bröcker EB, and Gillitzer R. Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma. A potential mechanism for high tumor aggressiveness. Am J Pathol 155: 753-763, 1999
57. Yamashita K, Discher DJ, Hu J, Bishopric NH, and Webster KA. Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, and p300/CBP. J Biol Chem 276: 12645-12653, 2001
58. Woo KJ, Lee TJ, Park JW, and Kwon TK. Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxy-genase-2 signaling pathway. Biochem Biophys Res Commun 343: 8-14, 2006
59. You JJ, Yang CM, Chen MS, and Yang CH. Regulation of Cyr61/CCN1 expression by hypoxia through cooperation of c-Jun/AP-1, and HIF-1α in retinal vascular endothelial cells. Exp Eye Res 91: 825-836, 2010
60. Chaqour B, and Goppelt-Struebe M. Mechanical regulation of the Cyr61/CCN1, and CTGF/CCN2 proteins. FEBS J 273: 3639 3649, 2006
61. Lee HY, Chung JW, Youn SW, Kim JY, Park KW, Koo BK, Oh BH, Park YB, Chaqour B, Walsh K, and Kim HS. Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation, and neointimal hyperplasia. Circ Res 100: 372-380, 2007
62. Chen CC, Chen N, and Lau LF. The angiogenic factors Cyr61, and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem 276: 10443-10452, 2001
63. Murphy LO, MacKeigan JP, and Blenis J. A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude, and duration. Mol Cell Biol 24: 144-153, 2004
64. Mo FE, Muntean AG, Chen CC, Stolz DB, Watkins SC, and Lau LF. CYR61 (CCN1) is essential for placental development, and vascular integrity. Mol Cell Biol 22: 8709-8720, 2002
65. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, and Simons JW. Overexpression of hypoxia-inducible factor 1alpha in common human cancers, and their metastases. Cancer Res 59: 5830-5835, 1999
66. Chaqour B. Molecular control of vascular development by the matricellular proteins CCN1 (Cyr61), and CCN2 (CTGF). Trends Dev Biol 7: 59-72, 2013