C/EBPγ regulates wound repair and EGF receptor signaling

Roberta Melchionna, Gabriella Bellavia, Marta Romani, Stefania Straino, Antonia Germani, Anna Di Carlo, Maurizio C. Capogrossi, Monica Napolitano

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1908-1917
Number of pages10
JournalJournal of Investigative Dermatology
Volume132
Issue number7
DOIs
Publication statusPublished - Jul 2012

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CCAAT-Enhancer-Binding Proteins
Epidermal Growth Factor Receptor
Repair
Wound Healing
Wounds and Injuries
Keratinocytes
Epidermal Growth Factor
Phosphorylation
RNA Interference
Small Interfering RNA
Cell Movement
Transcription Factors
Re-Epithelialization
Paxillin
Granulation
Granulation Tissue
Arterioles
Gene Silencing
Serum
Assays

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Melchionna, R., Bellavia, G., Romani, M., Straino, S., Germani, A., Di Carlo, A., ... Napolitano, M. (2012). C/EBPγ regulates wound repair and EGF receptor signaling. Journal of Investigative Dermatology, 132(7), 1908-1917. https://doi.org/10.1038/jid.2012.51

C/EBPγ regulates wound repair and EGF receptor signaling. / Melchionna, Roberta; Bellavia, Gabriella; Romani, Marta; Straino, Stefania; Germani, Antonia; Di Carlo, Anna; Capogrossi, Maurizio C.; Napolitano, Monica.

In: Journal of Investigative Dermatology, Vol. 132, No. 7, 07.2012, p. 1908-1917.

Research output: Contribution to journalArticle

Melchionna, R, Bellavia, G, Romani, M, Straino, S, Germani, A, Di Carlo, A, Capogrossi, MC & Napolitano, M 2012, 'C/EBPγ regulates wound repair and EGF receptor signaling', Journal of Investigative Dermatology, vol. 132, no. 7, pp. 1908-1917. https://doi.org/10.1038/jid.2012.51
Melchionna R, Bellavia G, Romani M, Straino S, Germani A, Di Carlo A et al. C/EBPγ regulates wound repair and EGF receptor signaling. Journal of Investigative Dermatology. 2012 Jul;132(7):1908-1917. https://doi.org/10.1038/jid.2012.51
Melchionna, Roberta ; Bellavia, Gabriella ; Romani, Marta ; Straino, Stefania ; Germani, Antonia ; Di Carlo, Anna ; Capogrossi, Maurizio C. ; Napolitano, Monica. / C/EBPγ regulates wound repair and EGF receptor signaling. In: Journal of Investigative Dermatology. 2012 ; Vol. 132, No. 7. pp. 1908-1917.
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