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Updated: Sep 25, 2026

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
10:42

Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Published on: December 22, 2017

Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor beta

Kenshi Yamasaki1, Nobuko Toriu, Yasushi Hanakawa

  • 1Department of Dermatology, Ehime University School of Medicine, Ehime, Japan. yamasaki@m.ehime-u.ac.jp

The Journal of Investigative Dermatology
|June 6, 2003
PubMed

Insights

High doses of epidermal growth factor (EGF) inhibit keratinocyte growth by activating an autocrine transforming growth factor beta1 (TGF-β1) pathway. This TGF-β1-ALK5 signaling acts as a negative feedback loop in normal human keratinocytes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • Epidermal growth factor receptor (EGFR) signaling regulates keratinocyte proliferation.
  • High-dose EGF ligands typically inhibit keratinocyte growth.
  • Previous studies implicated STAT1 in EGF-induced growth arrest in cancer cells, but not normal keratinocytes.

Purpose of the Study:

  • To investigate the role of transforming growth factor beta (TGF-β) in EGF-mediated keratinocyte growth inhibition.
  • To elucidate the signaling pathway involved in EGF-induced growth arrest in normal human keratinocytes.

Main Methods:

  • Stimulation of normal human keratinocytes with varying doses of EGF.
  • Measurement of TGF-β1 mRNA expression and protein levels.
  • Analysis of TGF-β-Smad signaling using a p3TP-lux reporter assay.
  • Inhibition of TGF-β type I receptor (ALK5) using an adenovirus vector (AxdnALK5).

Main Results:

  • EGF (10-100 ng/ml) significantly increased TGF-β1 mRNA and protein expression in keratinocytes.
  • EGF upregulated TGF-β-Smad signaling activity in a dose-dependent manner.
  • Inhibition of ALK5 blocked EGF-induced growth inhibition in normal keratinocytes.
  • EGF-induced TGF-β1 acts in an autocrine fashion.

Conclusions:

  • An autocrine TGF-β1-ALK5 pathway mediates EGF-induced growth inhibition in normal human keratinocytes.
  • This pathway serves as a negative feedback mechanism for EGF signaling.
  • Findings contrast with STAT1-dependent mechanisms observed in cancer cell lines.

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