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C/EBPγ regulates wound repair and EGF receptor signaling

Roberta Melchionna1, Gabriella Bellavia, Marta Romani

  • 1Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.

The Journal of Investigative Dermatology
|March 23, 2012
PubMed

Insights

CAAT enhancer-binding protein γ (C/EBPγ) is a key regulator of skin wound healing. Silencing C/EBPγ impaired skin repair in vitro and in vivo, affecting cell migration and EGFR signaling.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Skin wound healing (WH) is a complex process involving multiple cellular and molecular events.
  • Identifying novel regulators of WH is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To identify novel regulators of skin wound healing using a small interfering RNA (siRNA) silencing approach.
  • To characterize the role of CAAT enhancer-binding protein γ (C/EBPγ) in keratinocyte migration and skin repair.

Main Methods:

  • Epidermal scratch wound healing (WH) assay in keratinocytes.
  • siRNA-mediated gene silencing of transcription factors including C/EBPγ.
  • Assessment of keratinocyte migration, epidermal growth factor (EGF) and serum-induced signaling.
  • In vivo excisional wounding model in mice.

Main Results:

  • Silencing of C/EBPγ, STAT3, REL, RELA, RELB, SP1, and NFkB impaired WH in vitro.
  • C/EBPγ silencing maximally impaired scratch wounding (52.2 ± 12.5%) and inhibited EGF/serum-induced keratinocyte migration.
  • C/EBPγ overexpression enhanced keratinocyte migration via EGFR signaling.
  • C/EBPγ silencing reduced EGFR and paxillin phosphorylation and impaired WH in vivo, affecting re-epithelialization, granulation tissue formation, and arteriole number.

Conclusions:

  • C/EBPγ positively regulates skin wound healing both in vitro and in vivo.
  • C/EBPγ influences WH by modulating EGFR signaling pathways.
  • C/EBPγ is a potential therapeutic target for enhancing skin repair.

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