Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis
Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis
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DOI：
10.1111/wrr.12300
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发表时间：
2015-05-01
影响因子：
2.9
通讯作者：
Lee, Ju Hee
中科院分区：
文献类型：
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作者：
Lee, Won Jai;Park, Ji Hun;Lee, Ju Hee
内皮-间质转化是一种表型转换，其特征是血管内皮标记物下调和间质表型的获得。我们假设疤痕疙瘩成纤维细胞是内皮起源的，并且内皮到间质的转变在疤痕疙瘩的发生和进展过程中很大程度上促进了胶原蛋白的积累。使用免疫组织化学检查瘢痕疙瘩组织中无翼蛋白（Wnt-3a）的表达。用 Wnt-3a 处理人真皮微血管内皮细胞 (HDMEC)。分别使用实时 RT-PCR 和免疫细胞化学测量内皮（血管内皮钙粘蛋白）和间充质（波形蛋白、蜗牛家族转录因子 [slug] 和 平滑肌肌动蛋白）细胞标记物的 mRNA 和蛋白质表达。此外，使用免疫荧光检查了瘢痕疙瘩组织血管内皮中 CD31（分化簇 31）、内皮细胞标记物和波形蛋白的共表达。在人瘢痕疙瘩组织中观察到 Wnt-3a 过度表达。 Wnt-3a 处理显着降低 HDMEC 中血管内皮钙粘蛋白 mRNA 表达，并诱导波形蛋白和 slug mRNA 表达。 HDMEC 变成纺锤形，CD31 表达减少，波形蛋白、蛞蝓和平滑肌肌动蛋白表达增加。此外，在两名临床活动性瘢痕疙瘩患者的瘢痕疙瘩组织的真皮血管内皮中观察到CD31和波形蛋白的共表达。总之，HDMEC 向间充质表型的短暂转化可能导致疤痕疙瘩和肥厚性疤痕的真皮纤维化。
Endothelial-to-mesenchymal transition is a phenotypic conversion characterized by down-regulation of vascular endothelial markers and the acquisition of a mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial origin and that endothelial-to-mesenchymal transition substantially contributes to collagen accumulation during the development and progression of keloids. Wingless protein (Wnt-3a) protein expression was examined using immunohistochemistry in keloid tissues. Human dermal microvascular endothelial cells (HDMECs) were treated with Wnt-3a. mRNA and protein expression of endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail family transcription factor [slug], and -smooth muscle actin) cell markers were measured using real-time RT-PCR and immunocytochemistry, respectively. Additionally, coexpression of CD31 (cluster of differentiation 31), and endothelial cell marker, and vimentin in the vascular endothelium of keloid tissues was examined using immunofluorescence. Wnt-3a overexpression was observed in human keloid tissues. Wnt-3a treatment significantly reduced vascular endothelial cadherin mRNA expression and induced vimentin and slug mRNA expression in HDMECs. HDMECs became spindle-shaped and exhibited reduced expression of CD31 and increased expression of vimentin, slug, and -smooth muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the dermal vascular endothelium of keloid tissues from two patients with clinically active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars.