title: C/EBPγ regulates wound repair and EGF receptor signaling.
abstract: We aimed at identifying novel regulators of skin wound healing (WH), in an epidermal scratch WH assay, by a small interfering RNA (siRNA) silencing approach. Several transcription factors have been previously reported to affect wound repair. We here show that gene silencing of the transcription factor CAAT enhancer-binding protein γ (C/EBPγ), STAT3, REL, RELA, RELB, SP1, and NFkB impaired WH in vitro, in keratinocytes, whereas E2F and CREBBP silencing accelerated the WH process. We further characterized C/EBPγ, as its silencing yielded the maximal impairment (52.2 ± 12.5%) of scratch wounding (SW). We found that C/EBPγ silencing inhibited both EGF- and serum-induced keratinocyte migration, whereas C/EBPγ overexpression enhanced cell migration to EGF and to serum via the EGFR. Further, C/EBPγ silencing impaired scratch-induced Y1068 and Y1173 EGFR phosphorylation, as well as Y118 paxillin phosphorylation, key molecules regulating cell migration and epidermal WH. Moreover, C/EBPγ levels were induced in keratinocytes, following both SW and EGF stimulation. C/EBPγ siRNA silencing in vivo impaired WH at 3, 5, 7, and 14 days following excisional wounding in mice inhibited both re-epithelialization and granulation tissue formation, and induced a decrease of arteriole number. In conclusion, we here report that C/EBPγ positively regulates wound repair both in vitro and in vivo, at least in part, by affecting EGFR signaling.
authors.affiliation: Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Melchionna
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bellavia
authors.forename: Marta
authors.initials: M
authors.lastname: Romani
authors.forename: Stefania
authors.initials: S
authors.lastname: Straino
authors.forename: Antonia
authors.initials: A
authors.lastname: Germani
authors.forename: Anna
authors.initials: A
authors.lastname: Di Carlo
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Monica
authors.initials: M
authors.lastname: Napolitano
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; D016328:NF-kappa B; D051419:Paxillin; D034741:RNA, Small Interfering; D066246:ErbB Receptors