Cell proliferation and oxidative stress pathways are modified in fibroblasts from Sturge-Weber syndrome patients.

Sturge-Weber syndrome (SWS) is defined by vascular malformations of the face, eye and brain and an underlying somatic mutation has been hypothesized. We employed isobaric tags for relative and absolute quantification (iTRAQ-8plex)-based liquid chromatography interfaced with tandem mass spectrometry (LC-MS/MS) approach to identify differentially expressed proteins between port-wine-derived and normal skin-derived fibroblasts of four individuals with SWS. Proteins were identified that were significantly up- or down-regulated (i.e., ratios >1.2 or <0.8) in two or three pairs of samples (n = 31/972 quantified proteins) and their associated p values reported. Ingenuity pathway analysis (IPA) tool showed that the up-regulated proteins were associated with pathways that enhance cell proliferation; down-regulated proteins were associated with suppression of cell proliferation. The significant toxicologic list pathway in all four observations was oxidative stress mediated by Nrf2. This proteomics study highlights oxidative stress also consistent with a possible mutation in the RASA1 gene or pathway in SWS.