Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels

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 gamma 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 gamma 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 gamma subunit is activated in the most advanced stage of PWS and may participate in nodular formation.