2014
DOI: 10.1016/j.jaad.2014.07.025
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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… Show more

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Cited by 40 publications
(56 citation statements)
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“…We recently found the c-Jun N-terminal kinases (JNK) and extracellular signal regulated kinases (ERK) were consecutively activated in both infantile and adult PWS blood vessels. 4 Here we further identified that the GNAQ (R183Q) was primarily located within blood vessels in PWS lesions from 60% of our subjects, suggesting a causative correlation between GNAQ (R183Q) and activation of JNK and ERK in this subset of subjects under study. The reason for GNAQ (R183Q) occurrence in connective tissues and/or hair follicle/glands, but not blood vessels, in some subjects is unknown and requires further investigation.…”
Section: To the Editorsupporting
confidence: 63%
See 1 more Smart Citation
“…We recently found the c-Jun N-terminal kinases (JNK) and extracellular signal regulated kinases (ERK) were consecutively activated in both infantile and adult PWS blood vessels. 4 Here we further identified that the GNAQ (R183Q) was primarily located within blood vessels in PWS lesions from 60% of our subjects, suggesting a causative correlation between GNAQ (R183Q) and activation of JNK and ERK in this subset of subjects under study. The reason for GNAQ (R183Q) occurrence in connective tissues and/or hair follicle/glands, but not blood vessels, in some subjects is unknown and requires further investigation.…”
Section: To the Editorsupporting
confidence: 63%
“…The clinical histories of PWS biopsy samples were described in a previous study. 4 In order to identify which skin structure enriches the GNAQ (R183Q), we performed laser capture microscopy (LCM) to collect blood vessels and three other structures within PWS lesional skin, namely, epidermis, hair follicles/glands and connective tissues, on formalin-fixed paraffin embedded (FFPE) sections. An outline of LCM and DNA library construction is illustrated in Figure 1.…”
Section: To the Editormentioning
confidence: 99%
“…With immunohistochemical analysis of biopsies from PWS, we concluded that different protein kinases may be activated during different stages of PWS development [6]. Our data suggest that use of protein kinase inhibitors may serve as a potential therapeutic protocol for PWS.…”
Section: Future Research Directionsmentioning
confidence: 90%
“…We have identified an activation profile of various kinases during different stages of PWS progression, including (1) c-Jun N-terminal kinases and extracellular signal regulated kinases in infantile to nodular PWS, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinases, which may be involved in the progressive dilation of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit, which may lead to the formation of nodules [6]. Furthermore, PWS have elevated expression of both vascular endothelial growth factor (VEGF) and VEGF receptor subtype 2 (VEGFR-2) [7].…”
Section: Port-wine Stain Etiologymentioning
confidence: 99%
“…A sporadic somatic guanine nucleotide-binding protein, G alpha subunit q (GNAQ) mutation (R183Q), has been identified in PWS lesions with an average mutation frequency lower than 5%. 7,8 Tan et al have further found that the c-Jun N-terminal kinases and extracellular signal regulated kinases are consecutively activated in both infantile and adult PWS blood vessels, 9 which may partially be a result from GNAQ mutation (R183Q) in a subset of PWS patients. 10 The dilation of PWS blood vessels in patients is progressive with aging: PWS lesions are flat red macules in childhood, but become darken to purple, and often develop into vascular nodules by middle ages.…”
Section: Introductionmentioning
confidence: 99%