Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming

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Updated: Aug 8, 2026

Murine Dermal Fibroblast Isolation by FACS
06:04

Murine Dermal Fibroblast Isolation by FACS

Published on: January 7, 2016

T Chodon1, T Sugihara, H H Igawa

  • 1Department of Plastic and Reconstructive Surgery, Hokkaido University School of Medicine, Sapporo, Japan.

The American Journal of Pathology
|November 14, 2000
PubMed

Insights

Keloid fibroblasts resist apoptosis, unlike normal skin cells. Transforming growth factor-beta1 drives this resistance, suggesting new therapeutic targets for keloid treatment.

Area of Science:

  • Dermatology
  • Cell Biology
  • Wound Healing Research

Background:

  • Keloid pathogenesis is poorly understood, hindering effective therapeutic development.
  • Apoptosis (programmed cell death) is crucial for regulating cellularity during scar formation.
  • Current keloid treatments are limited, necessitating research into underlying mechanisms.

Purpose of the Study:

  • To investigate the role of apoptosis in keloid pathogenesis.
  • To compare the apoptotic response of keloid fibroblasts with hypertrophic scar and normal skin fibroblasts.
  • To identify molecular factors contributing to keloid fibroblast resistance to apoptosis.

Main Methods:

  • Fibroblast cultures derived from keloids, hypertrophic scars, and normal skin.
  • Induction of apoptosis using Fas-mediated and staurosporine-induced pathways.
  • Analysis of caspase activation and expression of apoptosis-related proteins (Fas, Bcl-2, Bax).
  • Assessment of transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 effects on apoptosis.

Main Results:

  • Keloid fibroblasts exhibited significant resistance to both Fas-mediated and staurosporine-induced apoptosis.
  • The apoptotic block in keloid cells occurred upstream of caspase activation.
  • Transforming growth factor-beta1 (TGF-beta1) significantly inhibited Fas-mediated apoptosis in normal and hypertrophic scar fibroblasts.
  • Neutralization of autocrine TGF-beta1 abrogated keloid fibroblast resistance, while TGF-beta2 had no anti-apoptotic effect.

Conclusions:

  • Keloid-derived fibroblasts possess a unique resistance to apoptosis, distinct from hypertrophic scar and normal skin fibroblasts.
  • The anti-apoptotic effect of TGF-beta1 plays a pivotal role in the refractory apoptosis observed in keloids.
  • Keloids should be considered a distinct entity from hypertrophic scars, and enhancing Fas-sensitivity presents a potential therapeutic strategy.

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