Rong Yin1,2,3, Shawn J Rice4, Jinwei Wang1,5, Lin Gao6, Joseph Tsai1, Radean T Anvari1, Fang Zhou1,5, Xin Liu4, Gang Wang6, Yuxin Tang5, Martin C Mihm7, Chandra P Belani4,8, Dong-Bao Chen9, J Stuart Nelson1,10, Wenbin Tan1,11. 1. Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California, Irvine, California, USA. 2. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina, USA. 3. Department of Dermatology, the Second Hospital of Shanxi Medical University, Taiyuan, China. 4. Penn State Cancer Institute, Hershey, PA, USA. 5. Department of Urology, the Xiangya 3rd Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. 6. Department of Dermatology, Xijing Hospital, Xi'an, China. 7. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 8. Department of Medicine, Penn State College of Medicine, Hershey, PA, USA. 9. Department of Obstetrics and Gynecology, University of California, Irvine, California, USA. 10. Department of Biomedical Engineering, University of California, Irvine, California, USA. 11. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina, USA. wenbin.tan@uscmed.sc.edu.
Abstract
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; 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. 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.
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; 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. 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.
Authors: G R Phillips; J K Huang; Y Wang; H Tanaka; L Shapiro; W Zhang; W S Shan; K Arndt; M Frank; R E Gordon; M A Gawinowicz; Y Zhao; D R Colman Journal: Neuron Date: 2001-10-11 Impact factor: 17.173
Authors: Eric W Deutsch; David Shteynberg; Henry Lam; Zhi Sun; Jimmy K Eng; Christine Carapito; Priska D von Haller; Natalie Tasman; Luis Mendoza; Terry Farrah; Ruedi Aebersold Journal: Proteomics Date: 2010-03 Impact factor: 3.984