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Targeting TWEAK/Fn14 pathway: Implications for stem cell regulation and advancements in skin disease therapies

Ahmad Taha Khalaf1, Xiaoming Liu2

  • 1Medical College, Anhui University of Science and Technology (AUST), Huainan 232001, China.

International Immunopharmacology
|October 25, 2025
PubMed

Insights

Tumor necrosis factor-like weak apoptosis-inducing factor (TWEAK) and its receptor Fn14 are crucial in cell regulation and disease. This pathway

Area of Science:

  • Immunology
  • Cell Biology
  • Dermatology

Background:

  • Tumor necrosis factor-like weak apoptosis-inducing factor (TWEAK) is a TNF superfamily member that signals through fibroblast growth factor-inducible 14 (Fn14).
  • This TWEAK/Fn14 pathway regulates critical cellular functions like proliferation, differentiation, and migration.
  • Dysregulation of TWEAK/Fn14 signaling is implicated in various diseases, including skin disorders and stem cell behavior.

Purpose of the Study:

  • To review the dual roles of TWEAK/Fn14 signaling in skin disease pathogenesis.
  • To examine the influence of TWEAK/Fn14 signaling on stem cell regulation.
  • To highlight the potential of TWEAK/Fn14 as a diagnostic biomarker and therapeutic target.

Main Methods:

  • Literature review of studies on TWEAK/Fn14 signaling.
  • Analysis of TWEAK/Fn14 involvement in skin disorders (e.g., lupus, psoriasis).
  • Investigation of TWEAK/Fn14 effects on stem cell behavior (liver, neural, mesenchymal).

Main Results:

  • TWEAK/Fn14 signaling is upregulated in skin diseases, contributing to fibroproliferation, angiogenesis, and inflammation.
  • Moderate TWEAK/Fn14 activation aids wound healing, while excessive activation causes pathological damage.
  • TWEAK/Fn14 influences stem cell proliferation and differentiation, impacting tissue repair and regeneration.

Conclusions:

  • The TWEAK/Fn14 pathway exhibits a dual role, promoting healing at moderate levels but causing damage when overactivated.
  • TWEAK/Fn14 signaling is a key factor in skin disease development and stem cell modulation.
  • Targeting the TWEAK/Fn14 pathway offers potential for early disease detection and novel therapeutic strategies in regenerative medicine and tissue engineering.
Keywords:
FibroproliferationSkin diseasesStem cell regulationTWEAK/Fn14 signaling

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