Study of gene correlation between endothelial growth factor family in mouse eye_Chinese Journal of Ocular Fundus Diseases

Authors：

Cui Jinglin ¹ ,  Lu Hang ¹ , Chen Jing ¹ , Luo Binjiang ¹ , Xiu Weiwei ¹ , Li Huimei ¹ , Huang Jiao ¹ , Chen Yuhan ² , Chen Jingyu ³

1. Department of Ophthalmology, The First Hospital of Qiqihar in Heilongjiang Province, Qiqihar 161005, China;
2. Guanganmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100053, China;
3. The First Clinical Medical College of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China;

Corresponding author：

Lu Hang, Email: luhangyanke@163.com

Keywords：

Vascular endothelial growth factors; DNA probes; Genome components

DOI：

10.3760/cma.j.cn511434-20180803-00269

Video：

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Objective To compare the function and action pathways of VEGFA, VEGFB and VEGFC in VEGF family of mouse eye.Methods Using the BXD mouse gene data in Genenetwork database as template to compare and study the similarities and differences of VEGFA, VEGFB and VEGFC molecular pathways or potential functions in the whole genome expression spectrum of BXD recombinant mouse inbred line population, with multiple analytical methods and statistical strategies were used, such as gene expression level, target genes comparison, top genes comparison associated to target genes, expression Quantitative Trait Loci (eQTL).Results Matrix comparison showed strong positive correlation between two probes of VEGFC (r=0.732, P＜0.01), weak correlation between VEGFA 1420909 and VEGFC 1440739, VEGFA 1451959 and VEGFC 1451803, VEGFC 1419417959 and VEGFC 1439766, VEGFC 1451803 and VEGFC 1439766 (P＜0.05); there was no correlation between VEGFA 1420909 and four other genes except VEGFC 1440739, VEGFA 1451959 and VEGFC 1440739, VEGFB 1451803 and VEGFA 1420909/VEGFC 1419417/VEGFC 1440739 (P ＞0.05). In the comparative analysis of the relevant Top₅₀ genes of each VEGF gene, most of the genes in BXD mouse were not significantly correlated with VEGFA, VEGFB and VEGFC except for the weak association of individual related genes. The results of eQTL analysis showed that each probe of VEGF gene was located on different chromosomes.Conclusions The expression levels and positive and negative correlations of VEGFA, VEGFB and VEGFC were different in the VEGF family of mouse eye, suggesting that these genes may play their role through different pathways.

Citation： Cui Jinglin, Lu Hang, Chen Jing, Luo Binjiang, Xiu Weiwei, Li Huimei, Huang Jiao, Chen Yuhan, Chen Jingyu. Study of gene correlation between endothelial growth factor family in mouse eye. Chinese Journal of Ocular Fundus Diseases, 2020, 36(3): 211-219. doi: 10.3760/cma.j.cn511434-20180803-00269 Copy

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15.	Zhong X, Huang H, Shen J, et al. Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation[J]. Mol Vis, 2011, 17: 492-507.
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18.	Autiero M, Waltenberger J, Communi D, et al. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1[J]. Nat Med, 2003, 9(7): 936-943. DOI: 10.1038/nm884.
19.	Enholm B, Karpanen T, Jeltsch M, et al. Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin[J]. Circ Res, 2001, 88(6): 623-629. DOI: 10.1161/01.res.88.6.623.
20.	Geisert EE, Lu L, Freeman-Anderson NE, et al. Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice[J]. Mol Vis, 2009, 15: 1730-1763.
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1. Gupta K, Zhang J. Angiogenesis: a curse or cure?[J]. Postgrad Med J, 2005, 81(954): 236-242. DOI: 10.1136/pgmj.2004.023309.
2. Chen S, Zhou M, Wang W, et al. Levels of angiogenesis-related vascular endothelial growth factor family in neovascular glaucoma eyes[J]. Acta Ophthalmol, 2015, 93(7): 556-560. DOI: 10.1111/aos.12624.
3. Penn JS, Madan A, Caldwell RB, et al. Vascular endothelial growth factor in eye disease[J]. Prog Retin Eye Res, 2008, 27(4): 331-371. DOI: 10.1016/j.preteyeres.2008.05.001.
4. Berg K, Pedersen TR, Sandvik L, et al. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol[J]. Ophthalmology, 2015, 122(1): 146-152. DOI: 10.1016/j.ophtha.2014.07.041.
5. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med, 2003, 9(6): 669-676. DOI: 10.1038/nm0603-669.
6. Houck KA, Ferrara N, Winer J, et al. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA[J]. Mol Endocrinol, 1991, 5(12): 1806-1814. DOI: 10.1210/mend-5-12-1806.
7. Cui J, Sun D, Lu H, et al. Comparison of effectiveness and safety between conbercept and ranibizumab for treatment of neovascular age-related macular degeneration: a retrospective case-controlled non-inferiority multiple center study[J]. Eye, 2018, 32(2): 391-399. DOI: 10.1038/eye.2017.187.
8. Wang L, Xiao J, Gu W, et al. Sex difference of EGFR expression and molecular pathway in the liver: impact on drug design and cancer treatments?[J]. J Cancer, 2016, 7(6): 671-680. DOI: 10.7150/jca.13684.
9. Wu CC, Huang HC, Juan HF, et al. GeneNetwork: an interactive tool for reconstruction of genetic networks using microarray data[J]. Bioinformatics, 2004, 20(18): 3691-3693. DOI: 10.1093/bioinformatics/bth428.
10. Jakeman LB, Armanini M, Phillips HS, et al. Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis[J]. Endocrinology, 1993, 133(2): 848-859. DOI: 10.1210/endo.133.2.7688292.
11. Li X, Eriksson U. Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D[J]. Int J Biochem Cell Biol, 2001, 33(4): 421-426. DOI: 10.1016/s1357-2725(01)00027-9.
12. Li X, Kumar A, Zhang F, et al. Complicated life, complicated VEGF-B[J]. Trends Mol Med, 2012, 18(2): 119-127. DOI: 10.1016/j.molmed.2011.11.006.
13. Nash AD, Baca M, Wright C, et al. The biology of vascular endothelial growth factor-B (VEGF-B)[J]. Pulm Pharmacol Ther, 2006, 19(1): 61-69. DOI: 10.1016/j.pupt.2005.02.007.
14. Zhang F, Tang Z, Hou X, et al. VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis[J]. Proc Natl Acad Sci USA, 2009, 106(5): 6152-6157. DOI: 10.1073/pnas.0813061106.
15. Zhong X, Huang H, Shen J, et al. Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation[J]. Mol Vis, 2011, 17: 492-507.
16. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice[J]. Science, 1997, 276(5317): 1423-1425. DOI: 10.1126/science.276.5317.1423.
17. Saaristo A, Veikkola T, Enholm B, et al. Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes[J]. FASEB J, 2002, 16(9): 1041-1049. DOI: 10.1096/fj.01-1042com.
18. Autiero M, Waltenberger J, Communi D, et al. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1[J]. Nat Med, 2003, 9(7): 936-943. DOI: 10.1038/nm884.
19. Enholm B, Karpanen T, Jeltsch M, et al. Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin[J]. Circ Res, 2001, 88(6): 623-629. DOI: 10.1161/01.res.88.6.623.
20. Geisert EE, Lu L, Freeman-Anderson NE, et al. Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice[J]. Mol Vis, 2009, 15: 1730-1763.
21. Lohela M, Bry M, Tammela T, et al. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis[J]. Curr Opin Cell Biol, 2009, 21(2): 154-165. DOI: 10.1016/j.ceb.2008.12.012.
22. Fuh G, Li B, Crowley C, et al. Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor[J]. J Biol Chem, 1998, 273(18): 11197-11204. DOI: 10.1074/jbc.273.18.11197.

Chinese Journal of Ocular Fundus Diseases

Study of gene correlation between endothelial growth factor family in mouse eye

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