Transcriptional Signature of Epidermal Keratinocytes Subjected toin VitroScratch Wounding Reveals Selective Roles for ERK1/2, p38, and Phosphatidylinositol 3-Kinase Signaling Pathways

摘要: Covering denuded dermal surfaces after injury requires migration, proliferation, and differentiation of skin keratinocytes. To clarify the major traits controlling these intermingled biological events, we surveyed genomic modifications occurring during course a scratch wound closure cultured human Using DNA microarray approach, report identification 161 new markers epidermal repair. Expression data, combined with functional analysis performed specific inhibitors ERK, p38(MAPK) phosphatidylinositol 3-kinase (PI3K), demonstrate that kinase pathways exert very selective functions by precisely expression genes. Inhibition ERK pathway totally blocks inactivates many early transcription factors EGF-type growth factors. inhibition only delays "healing," probably in line control genes involved propagation injury-initiated signaling. In contrast, PI3K accelerates potentiates scratch-dependent stimulation three related to epithelial cell transformation, namely HAS3, HBEGF, ETS1. Our results define vitro keratinocyte as repair process resulting from fine balance between positive signals controlled negative ones triggered PI3K. The perturbation any might lead dysfunction healing process, similar those observed pathological wounding phenotypes, such hypertrophic scars or keloids.