title: Transforming Growth Factor Beta Gene Signatures are Spatially Enriched in Keloid Tissue Biopsies and Ex vivo-Cultured Keloid Fibroblasts.
abstract: The keloid lesion is recognised as a spatially heterogeneous mass both in cellular and acellular composition and biological activity. Here, we have utilised a bioinformatic approach to determine whether this spatial heterogeneity is also evident at the molecular level and to identify key upstream regulators of signalling pathways enriched in the lesion in a spatially-restricted manner. Differentially expressed genes (20% change, p < 0.05) obtained from microarray datasets derived from whole keloid biopsies and ex vivo-cultured keloid fibroblasts, both from distinct regions of the keloid lesion (leading edge, centre, and top) have been analysed to show that the TGFβ family plays a significant but spatially dependent role in regulation of keloid gene expression. Furthermore, we have identified additional upstream signalling molecules involved in driving keloid biology and provide information on therapeutic targets whose modulation might be expected to lead to significant therapeutic efficacy.
authors.affiliation: BioPharm RD, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.forename: David C
authors.initials: DC
authors.lastname: Budd
authors.forename: Barbara
authors.initials: B
authors.lastname: Shih
authors.forename: Oliver
authors.initials: O
authors.lastname: Seifert
authors.forename: Andrew
authors.initials: A
authors.lastname: Beaton
authors.forename: Tracey
authors.initials: T
authors.lastname: Wright
authors.forename: Maria
authors.initials: M
authors.lastname: Dempsey
authors.forename: Fiona
authors.initials: F
authors.lastname: Kelly
authors.forename: Julia
authors.initials: J
authors.lastname: Egerton
authors.forename: Richard P
authors.initials: RP
authors.lastname: Marshall
authors.forename: Nicola
authors.initials: N
authors.lastname: Aston
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Bayat
mesh_terms: D001706:Biopsy; D002478:Cells, Cultured; D019295:Computational Biology; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007627:Keloid / Q000235:genetics*; D025341:Principal Component Analysis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta