Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels

• Rong Yin ^[4] ; Rice, Shawn J. ^[5] ; Jinwei Wang ^[4] ; Lin Gao ^[1] ; Joseph Tsai ^[4] ; Anvari, Radean T. ^[4] ; Fang Zhou ^[4] ; Xin Liu ^[5] ; Gang Wang ^[1] ; Yuxin Tang ^[2] ; Mihm Jr, Martin C. ^[3] ; Belani, Chandra P. ^[5] ; Chen, Dong-bao ^[6] ; Nelson, J. Stuart ^[4] ; Wenbin Tan ^[4]
  1. [1] Xijing Hospital

     Xijing Hospital

     China

     
  2. [2] Central South University

     Central South University

     China

     
  3. [3] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  4. [4] Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California, Irvine, California, USA
  5. [5] Penn State Cancer Institute, Hershey, Pennsylvania, USA
  6. [6] Department of Obstetrics and Gynecology, University of California, Irvine, California, USA

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 34, Nº. 5, 2019, págs. 479-490
• Idioma: inglés
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  • Introduction. 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.

    Methods. 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).

    Results. 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. Furthermore, TEM studies showed there is a significant upregulation of extracellular vesicle exocytosis from PWS blood vessels as compared to control.

    Conclusions. 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.