Wenbin Tan1, Margarita Chernova2, Lin Gao3, Victor Sun4, Huaxu Liu5, Wangcun Jia2, Stephanie Langer2, Gang Wang6, Martin C Mihm7, J Stuart Nelson4. 1. Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California. Electronic address: wenbint@uci.edu. 2. Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California-Irvine, Irvine, California. 3. 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. 4. 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. 5. Shandong Provincial Institute of Dermatology and Venereology, Jinan, Shandong, China. 6. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. 7. Department of Dermatology, Brigham and Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts.
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. 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.
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.
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