Advanced Glycation End Products Promote VEGF Expression and Thus Choroidal Neovascularization Via Cyr61-PI3K/AKT Signaling Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2017 Nov 4

PMID 29097668

Citations 20

Authors

Lijuan Sun

Tonglie Huang

Wenqin Xu

Jiaxing Sun

Yang Lv

Yusheng Wang

Affiliations

Soon will be listed here.

Abstract

Choroidal neovascularisation (CNV) causes severe vision loss among old patients, especially those with diabetes. Previously, Cyr61 has been found to play a critical role in the pathogenesis of both AMD and diabetes. In the present study, we found that increased CNV severity together with higher expression of Cyr61 and VEGF in diabetes mice compared with control mice. Moreover, knockdown of Cyr61 decreased CNV severity. In vitro mechanism study revealed that the advanced glycation end products (AGEs) significantly increased the expression of Cyr61 in retinal pigment epithelial (RPE) cells, mimicking the effects of diabetes. In turn, the increased Cyr61 enhanced VEGF expression through FAK and PI3K/Akt pathways. Chemically blocking the above pathway significantly inhibited CNV formation, providing a new strategy for clinical prevention and treatment of CNV in related diseases.

Citing Articles

Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.

Srejovic J, Muric M, Jakovljevic V, Srejovic I, Sreckovic S, Petrovic N Int J Mol Sci. 2024; 25(21).

PMID: 39519401 PMC: 11546760. DOI: 10.3390/ijms252111850.

Eye on the horizon: The metabolic landscape of the RPE in aging and disease.

Hansman D, Du J, Casson R, Peet D Prog Retin Eye Res. 2024; 104:101306.

PMID: 39433211 PMC: 11833275. DOI: 10.1016/j.preteyeres.2024.101306.

Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism.

Huang W, Liu X, Li X, Zhang R, Chen G, Mao X Front Endocrinol (Lausanne). 2024; 15:1438821.

PMID: 39387049 PMC: 11462413. DOI: 10.3389/fendo.2024.1438821.

Identification of key genes and biological pathways associated with vascular aging in diabetes based on bioinformatics and machine learning.

Wang S, Wang X, Chen J, Wang M, Zhang C Aging (Albany NY). 2024; 16(11):9369-9385.

PMID: 38809515 PMC: 11210242. DOI: 10.18632/aging.205870.

Targeting cell-type-specific, choroid-peripheral immune signaling to treat age-related macular degeneration.

Lin J, Santeford A, Colasanti J, Lee Y, Shah A, Wang T Cell Rep Med. 2024; 5(1):101353.

PMID: 38232696 PMC: 10829736. DOI: 10.1016/j.xcrm.2023.101353.

References

You J, Yang C, Chen M, Yang C . 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. 2010; 91(6):825-36. DOI: 10.1016/j.exer.2010.10.006. View

Kwon E, Park E, Choi S, Kim S, Cho M, Kim J . PPARγ agonist rosiglitazone inhibits migration and invasion by downregulating Cyr61 in rheumatoid arthritis fibroblast-like synoviocytes. Int J Rheum Dis. 2016; 20(10):1499-1509. DOI: 10.1111/1756-185X.12913. View

Giacomelli G, Finocchio L, Biagini I, Sodi A, Murro V, Introini U . Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment. Ophthalmologica. 2017; 238(1-2):44-51. DOI: 10.1159/000477498. View

Peiretti E, Caminiti G, Serra R, Querques L, Pertile R, Querques G . ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY VERSUS PHOTODYNAMIC THERAPY IN THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS CHORIORETINOPATHY. Retina. 2017; 38(8):1526-1532. DOI: 10.1097/IAE.0000000000001750. View

Augustin A, Offermann I . Combination therapy for choroidal neovascularisation. Drugs Aging. 2007; 24(12):979-90. DOI: 10.2165/00002512-200724120-00002. View

Yang X, Wang Y, Zhang J, Li Y, Xu J, Zhu J . 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. 2008; 50(4):1873-9. DOI: 10.1167/iovs.08-2591. View

You J, Yang C, Chen M, Yang C . Elevation of angiogenic factor Cysteine-rich 61 levels in vitreous of patients with proliferative diabetic retinopathy. Retina. 2011; 32(1):103-11. DOI: 10.1097/IAE.0b013e318219e4ad. View

Zhang F, Hao F, An D, Zeng L, Wang Y, Xu X . The matricellular protein Cyr61 is a key mediator of platelet-derived growth factor-induced cell migration. J Biol Chem. 2015; 290(13):8232-42. PMC: 4375479. DOI: 10.1074/jbc.M114.623074. View

Yoneyama S, Sakurada Y, Kikushima W, Sugiyama A, Tanabe N, Mabuchi F . GENETIC FACTORS ASSOCIATED WITH CHOROIDAL VASCULAR HYPERPERMEABILITY AND SUBFOVEAL CHOROIDAL THICKNESS IN POLYPOIDAL CHOROIDAL VASCULOPATHY. Retina. 2016; 36(8):1535-41. DOI: 10.1097/IAE.0000000000000964. View

10.

Chheda L, Ferketich A, Carroll C, Moyer P, Kurz D, Kurz P . Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome. Ophthalmology. 2011; 119(2):333-8. DOI: 10.1016/j.ophtha.2011.08.003. View

11.

Lau L . Cell surface receptors for CCN proteins. J Cell Commun Signal. 2016; 10(2):121-7. PMC: 4882306. DOI: 10.1007/s12079-016-0324-z. View

12.

Shi Y, Wang Y, Zhang Z, Cai Y, Zhou J, Hou H . Monocyte/macrophages promote vasculogenesis in choroidal neovascularization in mice by stimulating SDF-1 expression in RPE cells. Graefes Arch Clin Exp Ophthalmol. 2011; 249(11):1667-79. DOI: 10.1007/s00417-011-1699-4. View

13.

Cai Y, Li X, Wang Y, Shi Y, Ye Z, Yang G . Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells. Exp Eye Res. 2014; 123:87-96. DOI: 10.1016/j.exer.2014.04.012. View

14.

Leske M, Wu S, Hennis A, Nemesure B, Yang L, Hyman L . Nine-year incidence of age-related macular degeneration in the Barbados Eye Studies. Ophthalmology. 2005; 113(1):29-35. DOI: 10.1016/j.ophtha.2005.08.012. View

15.

Hou H, Liang H, Wang Y, Zhang Z, Wang B, Shi Y . A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions. Mol Ther. 2010; 18(10):1837-45. PMC: 2951561. DOI: 10.1038/mt.2010.144. View

16.

Li X, Cai Y, Wang Y, Shi Y, Hou W, Xu C . Hyperglycaemia exacerbates choroidal neovascularisation in mice via the oxidative stress-induced activation of STAT3 signalling in RPE cells. PLoS One. 2012; 7(10):e47600. PMC: 3477109. DOI: 10.1371/journal.pone.0047600. View

17.

Topouzis F, Anastasopoulos E, Augood C, Bentham G, Chakravarthy U, de Jong P . Association of diabetes with age-related macular degeneration in the EUREYE study. Br J Ophthalmol. 2009; 93(8):1037-41. DOI: 10.1136/bjo.2008.146316. View

18.

Xu T, He Y, Wang M, Yao H, Ni M, Zhang L . Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis. Gene. 2016; 592(1):179-185. DOI: 10.1016/j.gene.2016.07.053. View

19.

Hou J, Zheng D, Fung G, Deng H, Chen L, Liang J . Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats. Can J Physiol Pharmacol. 2016; 94(3):332-40. DOI: 10.1139/cjpp-2015-0073. View

20.

Kim J, Won C, Bak H, Kositratna G, Manstein D, Dotto G . Gene profiling analysis of the early effects of ablative fractional carbon dioxide laser treatment on human skin. Dermatol Surg. 2013; 39(7):1033-43. DOI: 10.1111/dsu.12170. View