软组织及椎体血管异常Tie2、Ang1、Ang2蛋白及mRNA的表达及临床意义
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摘要
目的探讨Tie2、Ang1、Ang2蛋白及mRNA在软组织及椎体血管异常(血管瘤和血管畸形)中的表达及其意义。方法收集血管异常110例,运用RT-PCR和免疫组化SP法检测Tie2、Ang1和Ang2在血管瘤及血管畸形中表达的差异,并进一步了解Tie2基因突变是否影响三者mRNA的表达。结果 Tie2、Ang1和Ang2 mRNA在血管瘤中的表达显著高于血管畸形(P<0.01);在血管瘤、软组织及椎体血管畸形中Ang2蛋白和mRNA的表达显著高于Ang1(P<0.05);突变型Tie2 mRNA的表达水平显著高于野生型(P<0.05),但伴Tie2基因突变的血管畸形Ang1和Ang2 mRNA的表达低于野生型血管畸形(P<0.05)。结论血管瘤和血管畸形可能为基因学改变不同的两种病变;Tie2基因突变、Ang1和Ang2的表达失衡可能促进血管异常病变进展。
Purpose To investigate the expression and clinical significance of Tie2,Ang1,Ang2 proteins and mRNA in soft tissue and vertebral vascular abnormalities( hemangiomas and vascular malformations). Methods 110 cases of vascular abnormalities were collected. The expression of Tie2,Ang1 and Ang2 in hemangiomas and vascular malformations( VMs) were detected by immunohistochemistry of SP method and RT-PCR,to explore whether Tie2 mutations affect the expression of Tie2,Ang1 and Ang2 mRNA. Results The expression of Tie2,Ang1 and Ang2 mRNA in hemangiomas was significantly higher than that in VMs( P < 0. 01). The expression of Ang2 protein and mRNA in hemangiomas,soft tissue and vertebral VMs was significantly higher than that of Ang1( P < 0. 05),and the expression of mutant Tie2 mRNA was significantly higher than wild type( P < 0. 05). However,the expression of Ang1 and Ang2 mRNA in VMs with Tie2 mutation was lower than that in wild type VMs( P < 0. 05). Conclusion Hemangiomas and VMs may be two lesions with different gene changes. Tie2 gene mutation and the expression imbalance of Ang1 and Ang2 may promote the development of vascular abnormalities.
Purpose To investigate the expression and clinical significance of Tie2,Ang1,Ang2 proteins and mRNA in soft tissue and vertebral vascular abnormalities( hemangiomas and vascular malformations). Methods 110 cases of vascular abnormalities were collected. The expression of Tie2,Ang1 and Ang2 in hemangiomas and vascular malformations( VMs) were detected by immunohistochemistry of SP method and RT-PCR,to explore whether Tie2 mutations affect the expression of Tie2,Ang1 and Ang2 mRNA. Results The expression of Tie2,Ang1 and Ang2 mRNA in hemangiomas was significantly higher than that in VMs( P < 0. 01). The expression of Ang2 protein and mRNA in hemangiomas,soft tissue and vertebral VMs was significantly higher than that of Ang1( P < 0. 05),and the expression of mutant Tie2 mRNA was significantly higher than wild type( P < 0. 05). However,the expression of Ang1 and Ang2 mRNA in VMs with Tie2 mutation was lower than that in wild type VMs( P < 0. 05). Conclusion Hemangiomas and VMs may be two lesions with different gene changes. Tie2 gene mutation and the expression imbalance of Ang1 and Ang2 may promote the development of vascular abnormalities.
引文
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[14]Fu Y,Yang Z G,Zhao L Y.Angiogenesis characteristics of infantile hemangioma and feasibility observation of transplantation model of human hemangioma on mice[J].Eur Rev Med Pharmacol Sci,2017,21(6):1276-1280.
[15]Limaye N,Wouters V,Uebelhoer M,et al.Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations[J].Nat Genet,2009,41(1):118-124.
[2]Zhou M,Jiang R B,Zhao G,et al.Classification and Tie2 mutations in spinal and soft tissue vascular anomalies[J].Gene,2015,571(1):91-96.
[3]Audero E,Cascone I,Maniero F,et al.Adaptor Shc A protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells[J].J Biol Chem,2004,279(13):13224-13233.
[4]Fagiani E,Christofori G.Angiopoietins in angiogenesis[J].Cancer Lett,2013,328(1):18-26.
[5]Sundberg C,Kowanetz M,Brown L F,et al.Stable expression of angiopoietin-1 and other markers by cultured pericytes:phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo[J].Lab Invest,2002,82(4):387-401.
[6]Makinde T,Agrawal D K.Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease[J].J Cell Mol Med,2008,12(3):810-828.
[7]Huang J,Inoue M,Hasegawa M,et al.Sendai viral vector mediated angiopoietin-1 gene transfer for experimental ischemic limb disease[J].Angiogenesis,2009,12(3):243-249.
[8]Xiao H,Huang Q,Wang J Q,et al.Effect of ephrin-B2 on the expressions of angiopoietin-1 and-2 after focal cerebral ischemia/reperfusion[J].Neural Regen Res,2016,11(11):1784-1789.
[9]Hashimoto T,Lam T,Boudreau N J,et al.Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations[J].Circ Res,2001,89(2):111-113.
[10]Perry B N,Govindarajan B,Bhandarkar S S,et al.Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice[J].J Invest Dermatol,2006,126(10):2316-2322.
[11]Illingworth R S,Bird A P.Cp G islands a rough guide[J].FEBS Lett,2009,583(11):1713-1720.
[12]Lee S G,Kim J L,Lee H K,et al.Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocininduced diabetes[J].Graefes Arch Clin Exp Ophthalmol,2011,249(3):389-397.
[13]Malik N M,Jin P,Raatz Y,et al.Regulation of the angiopoietinTie ligand-receptor system with a novel splice variant of Tie1 reduces the severity of murine arthritis[J].Rheumatology,2010,49(10):1828-1839.
[14]Fu Y,Yang Z G,Zhao L Y.Angiogenesis characteristics of infantile hemangioma and feasibility observation of transplantation model of human hemangioma on mice[J].Eur Rev Med Pharmacol Sci,2017,21(6):1276-1280.
[15]Limaye N,Wouters V,Uebelhoer M,et al.Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations[J].Nat Genet,2009,41(1):118-124.