title: Activation of PKCα and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions.
abstract: Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKCα, PI3K, PDPK1 and PLC-γ and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKCα, PI3K, PDPK1, and PLC-γ and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKCα and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.
authors.affiliation: *Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; †Departments of Dermatology, The Second Clinical Medical College, Shanxi Medical University, Taiyuan, China; ‡Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA; and §Department of Biomedical Engineering, University of California, Irvine, CA.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.forename: Wenbin
authors.initials: W
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.forename: Jhon Stuart
authors.initials: JS
authors.lastname: Nelson
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000201:enzymology / Q000473:pathology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019339:Port-Wine Stain / Q000201:enzymology* / Q000473:pathology*; D051571:Protein Kinase C-alpha / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha