VEGF promotes endothelial progenitor cell differentiation and vascular repair through connexin 43.
VEGF promotes endothelial progenitor cell differentiation and vascular repair through connexin 43.
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VEGF 通过连接蛋白 43 促进内皮祖细胞分化和血管修复
DOI：
10.1186/s13287-017-0684-1
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发表时间：
2017-10-24
影响因子：
7.5
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Li L;Liu H;Xu C;Deng M;Song M;Yu X;Xu S;Zhao X
背景内皮祖细胞（EPC）的分化是血管修复的关键。血管内皮生长因子（VEGF）诱导EPC分化，但这一现象的潜在机制尚不清楚。据报道，连接蛋白43（Cx43）参与干细胞分化的调节。因此，我们试图确定Cx43是否参与VEGF诱导的EPC分化和血管repair.MethodsRat脾来源的EPCs培养和治疗与不同浓度的VEGF（0，10，或50 ng/mL），EPC分化和Cx43表达之间的关系进行了评估。此后，进行光漂白后的荧光再分布，以评估相邻的EPC分化和Cx43诱导的间隙连接细胞间通讯（GJIC）之间的关系。颈动脉损伤后，将VEGF预处理的EPCs注入尾静脉，观察Cx43对血管修复的影响。结果VEGF诱导的EPCs分化加快，Cx43表达增加。然而，使用短干扰RNA（siRNA）抑制Cx43表达减弱了EPC GJIC和随后的EPC分化。血管内皮生长因子预处理的内皮祖细胞移植促进内皮祖细胞归巢和再内皮化，抑制新生内膜形成。Cx43的siRNA抑制可减弱上述作用。结论体内外实验结果表明VEGF通过Cx43促进EPC分化和血管修复。
BackgroundEndothelial progenitor cell (EPC) differentiation is considered crucial for vascular repair. Vascular endothelial growth factor (VEGF) induces EPC differentiation, but the underlying mechanism of this phenomenon remains unclear. Connexin 43 (Cx43) is reported to be involved in the regulation of stem cell differentiation. Therefore, we sought to determine whether Cx43 is involved in VEGF-induced EPC differentiation and vascular repair.MethodsRat spleen-derived EPCs were cultured and treated with various concentrations of VEGF (0, 10, or 50 ng/mL), and the relationship between EPC differentiation and Cx43 expression was evaluated. Thereafter, fluorescence redistribution after photobleaching was performed to assess the relationship between adjacent EPC differentiation and Cx43-induced gap junction intercellular communication (GJIC). After carotid artery injury, EPCs pretreated with VEGF were injected into the tail veins, and the effects of Cx43 on vascular repair were evaluated.ResultsEPCs cultured with VEGF exhibited accelerated differentiation and increased expression of Cx43. However, inhibition of Cx43 expression using short interfering RNA (siRNA) attenuated EPC GJIC and consequent EPC differentiation. VEGF-pretreated EPC transplantation promoted EPC homing and reendothelialization, and inhibited neointimal formation. These effects were attenuated by siRNA inhibition of Cx43.ConclusionsOur results from in vivo and in vitro experiments indicated that VEGF promotes EPC differentiation and vascular repair through Cx43.
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