血管内皮细胞生长抑制因子与眼科疾病的相关性_Chinese Journal of Ocular Fundus Diseases

Authors：

陈庆中 ,  颜华

300052 天津医科大学总医院眼科;

Corresponding author：

颜华, Email: phuayan2000@yahoo.com

Keywords：

视网膜疾病/病理生理学; 葡萄膜炎/病理生理学; 血管生成抑制剂; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.06.032

Video：

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Abstract Full text Figures/Tables Video References Cited by

血管内皮细胞生长抑制因子(VEGI)是一种多功能细胞因子, 可抑制血管生成、诱导细胞凋亡, 还能激活T细胞, 诱导树突状细胞分化而调节免疫反应。VEGI通过多种信号通路发挥其对内皮细胞的生物学效应, 且其抑制生长和诱导凋亡的作用发挥与内皮细胞的生长周期有关。目前已基本明确VEGI参与了炎症反应, 且与角膜新生血管、自身免疫性葡萄膜炎、糖尿病视网膜病变、青光眼、老年性黄斑变性和眼部肿瘤等眼科多种疾病的发生发展相关。进一步探讨VEGI与眼科疾病的相关性可能会为眼科疾病的病因学研究和治疗方法提供新的思路。

Citation： 陈庆中, 颜华. 血管内皮细胞生长抑制因子与眼科疾病的相关性. Chinese Journal of Ocular Fundus Diseases, 2014, 30(6): 640-643. doi: 10.3760/cma.j.issn.1005-1015.2014.06.032 Copy

1.	Zhai Y, Yu J, Iruela-Arispe L, et al.Inhibition of angiogenesis and breast cancer xenograft tumor growth by VEGI, a novel cytokine of the TNF superfamily[J]. Int J Cancer, 1999, 82:131-136.
2.	Chew LJ, Pan H, Yu J, et al.A novel secreted splice variant of vascular endothelial cell growth inhibitor[J]. FASEB J, 2002, 16:742-744.
3.	Jin T, Guo F, Kim S, et al.X-ray crystal structure of TNF ligand family member TL1A at 2.1A[J]. Biochem Biophys Res Commun, 2007, 364:1-6.
4.	Jin T, Kim S, Guo F, et al.Purificaion and crystallization of recombinant human TNF-like ligand TL1A[J]. Cytokine, 2007, 40:115-122.
5.	Migone TS, Zhang J, Luo X, et al.TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator[J]. Immunity, 2002, 16:479-492.
6.	Wen L, Zhuang L, Luo X, et al.TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells[J]. J Biol Chem, 2003, 278:39251-39258.
7.	Zhai Y, Ni J, Jiang G, et al.VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo[J]. FASEB J, 1999, 13:181-189.
8.	Kim S, Zhang L.Identification of naturally secreted soluble form of TL1A, a TNF-like cytokine[J]. J Immunol Methods, 2005, 298:1-8.
9.	Xiao Q, Hsu CY, Chen H, et al.Characterization of cis-regulatory elements of the vascular endothelial growth inhibitor gene promoter[J]. Biochem J, 2005, 388:913-920.
10.	Haridas V, Shrivastava A, Su J, et al.VEGI, a new member of the TNF family activates nuclear factor-kappaB and c-Jun N-terminal kinase and modulates cell growth[J]. Oncogene, 1999, 18:6496-6504.
11.	Gautam S, Bokyung S, Bharat B.Therapeutic potential of VEGI/TL1A in autoimmunity and cancer[J]. Adv Exp Med Biol, 2009, 647:207-215.
12.	Yue TL, Ni J, Romanic AM, et al.TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells.Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and Caspase-3-like protease[J]. J Biol Chem, 1999, 274:1479-1486.
13.	Yu J, Tian S, Metheny-Barlow L, et al.Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor[J]. Circ Rec, 2001, 89:1161-1167.
14.	Asahara T, Kawamoto A.Endothelial progenitor cells for postnatal vasculogenesis[J]. Am J Physiol Cell Physiol, 2004, 287:572-579.
15.	Bhatwadekar AD, Glenn JV, Li G, et al.Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells:implications for vasodegeneration in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2008, 49:1232-1241.
16.	Liang PH, Tian F, Lu Y, et al.Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors[J]. Angiogenesis, 2011, 14:61-68.
17.	Fang T, Liang PH, Li LY. Inhibition of endothelial progenitor cell differentiation by VEGI[J]. Blood, 2009, 113:5352-5360.
18.	Gupta N, Mansoor S, Sharma A, et al.Diabetic retinopathy and VEGF[J]. Open Ophthalmol J, 2013, 7:4-10.
19.	Bikfalvi A.Recent developments in the inhibition of angiogenesis:examples from studies on platelet factor-4 and the VEGF/VEGFR system[J]. Biochem Pharmacol, 2004, 68:1017-1021.
20.	Qi JW, Qin TT, Xu LX, et al.TNFSF15 inhibits vasculogenesis by regulating relative levels of membrane-bound and soluble isoforms of VEGF receptor 1[J]. Proc Natl Acad Sci USA, 2013, 110:13863-13868.
21.	Zhang N, Sanders AJ, Ye L, et al.Vascular endothelial growth inhibitor in human cancer[J]. Int J Mol Med, 2009, 24:3-8.
22.	Chang JH, Garg NK, Lunde E, et al.Corneal neovascularization:an anti-VEGF therapy review[J]. Surv Ophthalmol, 2012, 57:415-429.
23.	柳林, 刘银萍, 潘欣, 等.血管内皮细胞生长抑制因子VEGI151重组腺病毒对角膜新生血管的抑制作用[J].眼科研究, 2005, 23:245-248.
24.	王冰, 王传富, 王利华, 等.人血管内皮细胞生长抑制因子基因转移抑制角膜新生血管的实验研究[J].中华眼科杂志, 2008, 44:929-933.
25.	王冰, 王利华, 钟启文.不同浓度重组人pcDNA4-VEGI基因对角膜新生血管的抑制作用[J].眼科新进展, 2008, 28:516-519.
26.	Bjorn B, Taylor RS, Claus C.Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty:an evidence-based meta-analysis[J]. Ophthalmology, 2010, 117:1300-1305.
27.	Liu YP, Liu L, Pan DY, et al.Combined use of Ad-hENDO-VEGI151 and dexamethasone prevention and treatment of keratoplasty rejection:an experimental study[J]. J Med Coll PLA, 2006, 2186-2191.
28.	Qin TY.Upregulation of DR3 expression in CD4⁺ T cells promotes secretion of IL-17 in experimental autoimmune uveitis[J]. Mol Vis, 2011, 17:3486-3493.
29.	孙梅.调节性T细胞在实验性自身免疫性葡萄膜炎中的作用[J].临床眼科杂志, 2010, 18:467-470.
30.	Charles I, Khalyfa A, Kumar DM, et al.Serum deprivation induces apoptotic cell death of transformed rat retinal ganglion cells via mitochondrial signaling pathways[J]. Invest Ophthalmol Vis Sci, 2005, 46:1330-1338.
31.	Beg AA, Sha WC, Bronson RT, et al.Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB[J]. Nature, 1995, 376:167-170.
32.	Crawford MJ, Krishnamoorthy RR, Rudick VL, et al.Bcl-2 overexpression protects photooxidative stress-induced apoptosis of photoreceptor cells via NF-κB preservation[J]. Biochem Biophys Res Comm, 2001, 281:1304-1312.
33.	Kitson J, Raven T, Jiang YP, et al.A death-domain containing receptor that mediates apoptosis[J]. Nature, 1996, 384:372-375.
34.	Ashkenazi A, Dixit VM.Death receptors:signaling and modulation[J]. Science, 1998, 281:1305-1308.
35.	欧玉仑, 邝国平.新生血管性青光眼发病机制现状[J].国际眼科杂志, 2012, 12:1504-1506.
36.	Kumagai K, Furukawa M, Ogino N, et al.Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema[J]. Retina, 2009, 29:464-472.
37.	Bhadada SV, Goyal BR, Patel MM.Angiogenic targets for potential disorders[J]. Fundam Clin Pharmacol, 2011, 25:29-47.
38.	焦明菲, 颜华.糖尿病视网膜病变对大鼠循环外周血内皮祖细胞数量的影响[J].中华眼底病杂志, 2011, 27:250-254.
39.	张惟, 韩琪, 陈松, 等.增生型糖尿病视网膜病变患者外周血内皮祖细胞的数量变化及意义[J].中华眼底病杂志, 2011, 27:218-221.
40.	陈庆中, 张静楷, 黄利明, 等.血管内皮生长抑制因子在糖尿病视网膜病变患者血清及玻璃体中的变化[J].中华实验眼科杂志, 2013, 31:1163-1168.
41.	陈庆中, 江枫, 毛春洁, 等.血管内皮生长抑制因子在糖尿病视网膜病变大鼠中的表达[J].中华眼底病杂志, 2014, 30:180-186.
42.	Hou HY, Liang HL, Wang YS.Bone marrow-derived cells in neovascular age-related macular degeneration:contribution and potential application[J]. Ophthalmic Res, 2010, 45:1-4.
43.	Wang YJ, Shen DF, Vinson M, et al.Enhanced apoptosis in retinal pigment epithelium under inflammatory simuli and oxidative stress[J]. Apoptosis, 2012, 17:1144-1155.
44.	Kim B, Tang Q, Biswas PS, et al.Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes:therapeutic strategy for herpetic stromal keratitis[J]. Am J Pathol, 2004, 165:2177-2185.
45.	杨秀梅, 王雨生, 惠延年.外源性脉络膜新生血管抑制剂的研究进展[J].眼科新进展, 2005, 25:75-78.
46.	Pan X, Wang Y, Zhang M, et al.Effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenoviruses on antiangiogenesis[J]. World J Gastroenterol, 2004, 10:1409-1414.
47.	Hou W, Medynski D, Wu S, et al.VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth[J]. Clin Cancer Res, 2005, 11:5595-5602.
48.	罗丹, 方玉华, 彭洁.反义VEGF基因转染对视网膜母细胞瘤细胞VEGF表达的影响[J].眼科新进展, 2005, 25:338-340.
49.	Siffroi-Fernandez S, Cinaroglu A, Fuhrmann-Panfalone V, et al.Acidic fibroblast growth factor (FGF-1) and FGF receptor 1 signaling in human Y 79 retinoblastoma[J]. Arch Ophthalmol, 2005, 123:368-376.
50.	Chen D, Pajovic S, Duckett A, et al.Genomic amplification in retinoblastoma a narrowed to 0.6m egabase on chromosome 6p containing a kinesin-like gene, RBKIN[J]. Cancer Res, 2002, 15:967-971.
51.	Wsters JS, Webb A, Cunningham D. Phase Ⅰ clinical and phamacokinetic study of Bcl-2 antisense oligonu cleotide therapy in patients with non-Hodgkin's lymphoma[J]. Clin Oncol, 2000, 18:1812-1823.
52.	富名水, 张皙, 邱庆华, 等.EGFR反义寡核苷酸对人视网膜神经胶质细胞增生的影响[J].眼科新进展, 2002, 22:239-241.

1. Zhai Y, Yu J, Iruela-Arispe L, et al.Inhibition of angiogenesis and breast cancer xenograft tumor growth by VEGI, a novel cytokine of the TNF superfamily[J]. Int J Cancer, 1999, 82:131-136.
2. Chew LJ, Pan H, Yu J, et al.A novel secreted splice variant of vascular endothelial cell growth inhibitor[J]. FASEB J, 2002, 16:742-744.
3. Jin T, Guo F, Kim S, et al.X-ray crystal structure of TNF ligand family member TL1A at 2.1A[J]. Biochem Biophys Res Commun, 2007, 364:1-6.
4. Jin T, Kim S, Guo F, et al.Purificaion and crystallization of recombinant human TNF-like ligand TL1A[J]. Cytokine, 2007, 40:115-122.
5. Migone TS, Zhang J, Luo X, et al.TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator[J]. Immunity, 2002, 16:479-492.
6. Wen L, Zhuang L, Luo X, et al.TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells[J]. J Biol Chem, 2003, 278:39251-39258.
7. Zhai Y, Ni J, Jiang G, et al.VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo[J]. FASEB J, 1999, 13:181-189.
8. Kim S, Zhang L.Identification of naturally secreted soluble form of TL1A, a TNF-like cytokine[J]. J Immunol Methods, 2005, 298:1-8.
9. Xiao Q, Hsu CY, Chen H, et al.Characterization of cis-regulatory elements of the vascular endothelial growth inhibitor gene promoter[J]. Biochem J, 2005, 388:913-920.
10. Haridas V, Shrivastava A, Su J, et al.VEGI, a new member of the TNF family activates nuclear factor-kappaB and c-Jun N-terminal kinase and modulates cell growth[J]. Oncogene, 1999, 18:6496-6504.
11. Gautam S, Bokyung S, Bharat B.Therapeutic potential of VEGI/TL1A in autoimmunity and cancer[J]. Adv Exp Med Biol, 2009, 647:207-215.
12. Yue TL, Ni J, Romanic AM, et al.TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells.Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and Caspase-3-like protease[J]. J Biol Chem, 1999, 274:1479-1486.
13. Yu J, Tian S, Metheny-Barlow L, et al.Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor[J]. Circ Rec, 2001, 89:1161-1167.
14. Asahara T, Kawamoto A.Endothelial progenitor cells for postnatal vasculogenesis[J]. Am J Physiol Cell Physiol, 2004, 287:572-579.
15. Bhatwadekar AD, Glenn JV, Li G, et al.Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells:implications for vasodegeneration in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2008, 49:1232-1241.
16. Liang PH, Tian F, Lu Y, et al.Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors[J]. Angiogenesis, 2011, 14:61-68.
17. Fang T, Liang PH, Li LY. Inhibition of endothelial progenitor cell differentiation by VEGI[J]. Blood, 2009, 113:5352-5360.
18. Gupta N, Mansoor S, Sharma A, et al.Diabetic retinopathy and VEGF[J]. Open Ophthalmol J, 2013, 7:4-10.
19. Bikfalvi A.Recent developments in the inhibition of angiogenesis:examples from studies on platelet factor-4 and the VEGF/VEGFR system[J]. Biochem Pharmacol, 2004, 68:1017-1021.
20. Qi JW, Qin TT, Xu LX, et al.TNFSF15 inhibits vasculogenesis by regulating relative levels of membrane-bound and soluble isoforms of VEGF receptor 1[J]. Proc Natl Acad Sci USA, 2013, 110:13863-13868.
21. Zhang N, Sanders AJ, Ye L, et al.Vascular endothelial growth inhibitor in human cancer[J]. Int J Mol Med, 2009, 24:3-8.
22. Chang JH, Garg NK, Lunde E, et al.Corneal neovascularization:an anti-VEGF therapy review[J]. Surv Ophthalmol, 2012, 57:415-429.
23. 柳林, 刘银萍, 潘欣, 等.血管内皮细胞生长抑制因子VEGI151重组腺病毒对角膜新生血管的抑制作用[J].眼科研究, 2005, 23:245-248.
24. 王冰, 王传富, 王利华, 等.人血管内皮细胞生长抑制因子基因转移抑制角膜新生血管的实验研究[J].中华眼科杂志, 2008, 44:929-933.
25. 王冰, 王利华, 钟启文.不同浓度重组人pcDNA4-VEGI基因对角膜新生血管的抑制作用[J].眼科新进展, 2008, 28:516-519.
26. Bjorn B, Taylor RS, Claus C.Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty:an evidence-based meta-analysis[J]. Ophthalmology, 2010, 117:1300-1305.
27. Liu YP, Liu L, Pan DY, et al.Combined use of Ad-hENDO-VEGI151 and dexamethasone prevention and treatment of keratoplasty rejection:an experimental study[J]. J Med Coll PLA, 2006, 2186-2191.
28. Qin TY.Upregulation of DR3 expression in CD4⁺ T cells promotes secretion of IL-17 in experimental autoimmune uveitis[J]. Mol Vis, 2011, 17:3486-3493.
29. 孙梅.调节性T细胞在实验性自身免疫性葡萄膜炎中的作用[J].临床眼科杂志, 2010, 18:467-470.
30. Charles I, Khalyfa A, Kumar DM, et al.Serum deprivation induces apoptotic cell death of transformed rat retinal ganglion cells via mitochondrial signaling pathways[J]. Invest Ophthalmol Vis Sci, 2005, 46:1330-1338.
31. Beg AA, Sha WC, Bronson RT, et al.Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB[J]. Nature, 1995, 376:167-170.
32. Crawford MJ, Krishnamoorthy RR, Rudick VL, et al.Bcl-2 overexpression protects photooxidative stress-induced apoptosis of photoreceptor cells via NF-κB preservation[J]. Biochem Biophys Res Comm, 2001, 281:1304-1312.
33. Kitson J, Raven T, Jiang YP, et al.A death-domain containing receptor that mediates apoptosis[J]. Nature, 1996, 384:372-375.
34. Ashkenazi A, Dixit VM.Death receptors:signaling and modulation[J]. Science, 1998, 281:1305-1308.
35. 欧玉仑, 邝国平.新生血管性青光眼发病机制现状[J].国际眼科杂志, 2012, 12:1504-1506.
36. Kumagai K, Furukawa M, Ogino N, et al.Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema[J]. Retina, 2009, 29:464-472.
37. Bhadada SV, Goyal BR, Patel MM.Angiogenic targets for potential disorders[J]. Fundam Clin Pharmacol, 2011, 25:29-47.
38. 焦明菲, 颜华.糖尿病视网膜病变对大鼠循环外周血内皮祖细胞数量的影响[J].中华眼底病杂志, 2011, 27:250-254.
39. 张惟, 韩琪, 陈松, 等.增生型糖尿病视网膜病变患者外周血内皮祖细胞的数量变化及意义[J].中华眼底病杂志, 2011, 27:218-221.
40. 陈庆中, 张静楷, 黄利明, 等.血管内皮生长抑制因子在糖尿病视网膜病变患者血清及玻璃体中的变化[J].中华实验眼科杂志, 2013, 31:1163-1168.
41. 陈庆中, 江枫, 毛春洁, 等.血管内皮生长抑制因子在糖尿病视网膜病变大鼠中的表达[J].中华眼底病杂志, 2014, 30:180-186.
42. Hou HY, Liang HL, Wang YS.Bone marrow-derived cells in neovascular age-related macular degeneration:contribution and potential application[J]. Ophthalmic Res, 2010, 45:1-4.
43. Wang YJ, Shen DF, Vinson M, et al.Enhanced apoptosis in retinal pigment epithelium under inflammatory simuli and oxidative stress[J]. Apoptosis, 2012, 17:1144-1155.
44. Kim B, Tang Q, Biswas PS, et al.Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes:therapeutic strategy for herpetic stromal keratitis[J]. Am J Pathol, 2004, 165:2177-2185.
45. 杨秀梅, 王雨生, 惠延年.外源性脉络膜新生血管抑制剂的研究进展[J].眼科新进展, 2005, 25:75-78.
46. Pan X, Wang Y, Zhang M, et al.Effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenoviruses on antiangiogenesis[J]. World J Gastroenterol, 2004, 10:1409-1414.
47. Hou W, Medynski D, Wu S, et al.VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth[J]. Clin Cancer Res, 2005, 11:5595-5602.
48. 罗丹, 方玉华, 彭洁.反义VEGF基因转染对视网膜母细胞瘤细胞VEGF表达的影响[J].眼科新进展, 2005, 25:338-340.
49. Siffroi-Fernandez S, Cinaroglu A, Fuhrmann-Panfalone V, et al.Acidic fibroblast growth factor (FGF-1) and FGF receptor 1 signaling in human Y 79 retinoblastoma[J]. Arch Ophthalmol, 2005, 123:368-376.
50. Chen D, Pajovic S, Duckett A, et al.Genomic amplification in retinoblastoma a narrowed to 0.6m egabase on chromosome 6p containing a kinesin-like gene, RBKIN[J]. Cancer Res, 2002, 15:967-971.
51. Wsters JS, Webb A, Cunningham D. Phase Ⅰ clinical and phamacokinetic study of Bcl-2 antisense oligonu cleotide therapy in patients with non-Hodgkin's lymphoma[J]. Clin Oncol, 2000, 18:1812-1823.
52. 富名水, 张皙, 邱庆华, 等.EGFR反义寡核苷酸对人视网膜神经胶质细胞增生的影响[J].眼科新进展, 2002, 22:239-241.

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血管内皮细胞生长抑制因子与眼科疾病的相关性

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