title: Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels.
abstract: BACKGROUND
  Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood.
  
  
  OBJECTIVE
  We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues.
  
  
  METHODS
  Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS.
  
  
  RESULTS
  c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels.
  
  
  CONCLUSIONS
  Infantile PWS sample size was small.
  
  
  CONCLUSIONS
  Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation.
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California. Electronic address: wenbint@uci.edu.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California.
authors.forename: Margarita
authors.initials: M
authors.lastname: Chernova
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California; Department of Biomedical Engineering, University of California-Irvine, Irvine, California.
authors.forename: Victor
authors.initials: V
authors.lastname: Sun
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Jinan, Shandong, China.
authors.forename: Huaxu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California.
authors.forename: Wangcun
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Langer
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California; Department of Biomedical Engineering, University of California-Irvine, Irvine, California.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D001808:Blood Vessels / Q000201:enzymology*; D002675:Child, Preschool; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D019339:Port-Wine Stain / Q000201:enzymology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma
keywords: AKT; c-Jun N-terminal kinase; extracellular signal-regulated kinase; mitogen-activated protein kinase; port-wine stain; vascular malformation