The JAK–STAT pathway in keloid pathogenesis: a systematic review with qualitative synthesis

Qi Yin*, Albert Wolkerstorfer, Oren Lapid, Frank B. Niessen, Paul P.M. Van Zuijlen, Susan Gibbs

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review

Abstract

Keloid tissues contain inflammatory cells and upregulated pro-inflammatory cytokines. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediate cellular responses to these cytokines. We performed a systematic review on the role of the JAK–STAT pathway in keloid pathogenesis and the evidence for JAK–STAT inhibitors in keloid treatment. The search combined the terms (1) keloid and (2) JAK or TYK or STAT and included MeSH terms and synonyms. Two reviewers screened the articles and assessed the full texts on eligibility. Data were collected on the tested drugs and molecules, the type of cells and tissues used in the experiments, and study findings on the association between the JAK–STAT pathway and keloid cells and tissues. A total of twenty preclinical studies were included. Eleven preclinical studies proved that STAT3 expression and phosphorylation are enhanced in keloid tissue and keloid fibroblasts. Thirteen different JAK and/or STAT inhibitors were investigated. Tested drugs inhibited keloid progression as demonstrated by different processes, including reduced collagen production, cell proliferation and migration, increased cell cycle arrest and apoptosis, enhanced antioxidant responses, decreased (paracrine) signalling, and decreased profibrotic gene expression. No clinical studies have been published to date. Preclinical studies indicate a role for the JAK–STAT pathway in keloid pathogenesis and a potential role for JAK–STAT inhibitors in keloid treatment. The effect of these drugs should be further investigated on relevant biomarkers in a human keloid skin model, preferably including immune cells besides keloid fibroblasts and keratinocytes and in clinical studies.

Original languageEnglish
Pages (from-to)588-598
Number of pages11
JournalExperimental Dermatology
Volume32
Issue number5
Early online date18 Jan 2023
DOIs
Publication statusPublished - May 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.

Keywords

  • JAK
  • Janus kinase
  • keloid
  • signal transducer and activator of transcription
  • STAT

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