Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.
Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.
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DOI：
10.14670/hh-18-051
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发表时间：
2019-05
影响因子：
2
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Yin R;Rice SJ;Wang J;Gao L;Tsai J;Anvari RT;Zhou F;Liu X;Wang G;Tang Y;Mihm MC Jr;Belani CP;Chen DB;Nelson JS;Tan W
葡萄酒染色（PWS）的特点是由于内皮细胞分化受损导致的未成熟小静脉样血管的进行性扩张。在本研究中，我们旨在确定PWS发病机制的主要生物学途径。采用顺序窗口获取所有理论片段离子质谱（SWATH-MS）来鉴定PWS病变中的差异表达蛋白，随后采用免疫组织化学、免疫印迹和透射电镜（TEM）进行确证研究。299种鉴定的蛋白中有107种在PWS病变中与正常皮肤有差异表达，主要涉及生物合成、膜运输、细胞骨架和细胞粘附/迁移等功能。证实性研究表明，与正常血管相比，PWS血管中VAT1、IQGAP1、HSC70、网格蛋白、perlecan、spectrin α1、GDIR1等膜转运/胞吐相关蛋白的表达显著升高；PWS皮肤中胶原蛋白亚型6A1和6A3减少。此外，透射电镜研究显示，与对照组相比，PWS血管的细胞外囊泡胞吐明显上调。膜运输和胞吐的生物学过程在PWS血管中增强。我们的研究结果提示病变内皮细胞释放的细胞外囊泡可能作为潜在的细胞间信号介质参与PWS的发病机制。
Port wine stain (PWS) is characterized as a progressive dilatation of immature venule-like vasculatures which result from differentiation-impaired endothelial cells. In this study, we aimed to identify the major biological pathways accounting for the pathogenesis of PWS. Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) was used to identify differentially expressed proteins in PWS lesions, followed by confirmative studies with immunohistochemistry, immunoblot and transmission electron microscopy (TEM). 107 out of 299 identified proteins showed differential expressions in PWS lesions as compared to normal skin, mainly involving the functions of biosynthesis, membrane trafficking, cytoskeleton and cell adhesion/migration. The confirmative studies showed that expressions of membrane trafficking/exocytosis related proteins such as VAT1, IQGAP1, HSC70, clathrin, perlecan, spectrin α1 and GDIR1 were significantly increased in PWS blood vessels as compared to normal ones; while collagen subtypes 6A1 and 6A3 were decreased in PWS skin. Furthermore, TEM studies showed there is a significant upregulation of extracellular vesicle exocytosis from PWS blood vessels as compared to control. The biological process of membrane trafficking and exocytosis is enhanced in PWS blood vessels. Our results imply that the extracellular vesicles released by lesional endothelial cells may act as potential intercellular signaling mediators to contribute to the pathogenesis of PWS.