Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels - 16/10/14
, Margarita Chernova, BS a, Lin Gao, MD, PhD a, d, Victor Sun, MS a, b, Huaxu Liu, MD, PhD e, Wangcun Jia, PhD a, Stephanie Langer, MD a, Gang Wang, MD, PhD d, Martin C. Mihm, MD c, J. Stuart Nelson, MD, PhD a, bAbstract |
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.
Limitation |
Infantile PWS sample size was small.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : AKT, c-Jun N-terminal kinase, extracellular signal-regulated kinase, mitogen-activated protein kinase, port-wine stain, vascular malformation
Abbreviations used : ERK, JNK, PI3K, PLC-γ, PWS
Plan
| Supported by National Institutes of Health AR063766 (Dr Tan), AR47551 (Dr Nelson), and AR59244 (Dr Nelson), and the American Society for Laser Medicine and Surgery research grant F03.12 and F01.13 (Dr Tan). |
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| Conflicts of interest: None declared. |
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| Reprints not available from the authors. |
Vol 71 - N° 5
P. 964-968 - novembre 2014 Retour au numéro
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