PTEN对婴幼儿血管瘤内皮细胞VEGF-A／VEGFR-2自分泌环的调控作用  

Modulating effects of PTEN in the loop of autocrine VEGF-A/VEGFR-2 in hemangioma-derived cells

作　　者：王川[1] 向波[1] 陈思源[2] 吉毅[1] Wang Chuan Xiang Bo Chen Siyuan Ji Yi(Department of Pediatric Surgery Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China)

机构地区：[1]四川大学华西医院小儿外科,成都610041 [2]四川大学华西医院重症医学科儿童重症监护室,成都610041

出　　处：《中华小儿外科杂志》2017年第1期16-19,共4页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金资助项目（81401606、81400862）;四川大学优秀青年学者基金（2015SU04A15）

摘　　要：目的研究PTEN在婴幼儿血管瘤（infantile hemangioma，IH）中的表达，探讨其对血管瘤内皮细胞（HemEC）中VEGF-A／VEGFR-2自分泌环的影响与意义。方法应用Real-timePCR检测增殖期IH组织与正常皮肤组织中PTEN基因表达差异，Westernblot检测HemEC与正常血管内皮细胞中PTEN蛋白水平。采用腺病毒瞬时转染构建立PTEN高表达HemEC模型，观察PTEN表达变化对HemEC中VEGF-A、VEGFR-2与磷酸化VEGFR-2表达水平的影响，分析PTEN表达变化对HemEC增殖与凋亡的影响。结果PTEN基因在IH微血管组织中的表达较正常皮肤血管组织出现显著的下调。通过对HemEC中FrrEN蛋白表达量进行检测发现，与异常活化的VEGF-A／VEGFR-2信号通路相反，HemEC中PTEN蛋白表达较正常血管内皮细胞低（0．08±0．02比1．86±0．41）。PTEN高表达可显著抑制VEGF的表达，并抑制VEGF-A对VEGFR-2磷酸化的激活（1．27±0．25比0．09±0．03），但对VEGFR-2蛋白表达水平无显著作用（2．32±0．51比2．35±0．42）。上调PTEN后HemEC增殖能力显著降低、凋亡率显著升高。结论PTEN通过对HemEC中VEGF-A／VEGFR-2自分泌环的调控，从而影响HemEC的增殖和凋亡状态。Objective To explore the expression of PTEN in infantile hemangioma （IH） and determine its involvement in the regulation of VEGF-A/VEGFR-2 loop of hemangioma-derived endothelial cells （HemECs）. Methods Real-time polymerase chain reaction （PCR） was performed for evaluating the expression of PTEN in proliferating IH tissues and normal skin. Protein expressions of PTEN in HemECs and normal endothelial cells （ECs） were assayed by Western blot. And the effects of PTEN were also analyzed in regulating HemEC proliferation and apoptosis. Results The expression of tumor suppressor PTEN decreased in proliferating IH tissues as compared with normal skin. As compared with normal＇ endothelial cells （HUVECs）, HemECs showed a down-regulation of PTEN protein （0. 08 ± 0. 02 vs 1.86 ± 0. 41 ）. The expression of endogenous VEGF and activation of VEGFR- 2 decreased markedly in PTEN-transfected HemECs as compared with control ceils （1.27 ± 0. 25 vs 0. 09 ± 0. 03）. In contrast, there was no significant effect of PTEN on VEGFR-2 expression （2. 32 ± 0. 51 vs 2. 35 ± 0. 42）. An up-regulation of PTEN decreased HemEC proliferation and caused heightened sensitivity to apoptosis in HemEcs. Conclusions PTEN prevents the activation of VEGF- A/VEGFR-2 loop in HemECs. Also it is capable of inhibiting HemECs proliferation and inducing HemECs apoptosis in vitro.

关 键 词：血管瘤 内皮细胞 血管内皮细胞生长因子 

分 类 号：R732.2[医药卫生—肿瘤]