Evidence For a Fibrogenic Interaction Between the Aryl Hydrocarbon Receptor and the Wnt/β-Catenin Pathways in Human Keratinocytes and Fibroblasts

  • Cell Physiol Biochem. 2026 Jan 30;60(1):44-62. doi: 10.33594/000000846.
Anna Wajda  1 ,  Adam Ejma-Multański  1 ,  Dina Himida  2 ,  Barbara Stypińska  1 ,  Gabriela Filipowicz  1 ,  Andrea Rossi  2 ,  Inken Hacheney  2 ,  Thomas Haarmann-Stemmann  2 ,  Agnieszka Paradowska-Gorycka  1 ,  Charlotte Esser  2
Affiliations
  • 1. Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
  • 2. IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
PMID: 41668603 DOI: 10.33594/000000846
Abstract

Background/aims: Systemic sclerosis is a rare autoimmune and fibrotic disease, often manifesting in the skin. The Aryl Hydrocarbon Receptor is critical for skin homeostasis; however, its role in fibrosis is not well understood. We investigated the crosstalk between TGFβ, AHR, and Wnt/β-catenin signaling.

Methods: Human dermal fibroblasts and HaCaT keratinocytes, both wild-type and AHR-deficient, were cultured in mono- and co-cultures. Cells were treated with TGFβ and the AHR agonist FICZ. Collagen type I and MMP1 were quantified, Wnt/β-catenin genes analyzed, migration assessed, and proteome profiling performed.

Results: AHR deletion reduced Wnt/β-catenin gene expression and abrogated TGFβ-induced Collagen production. Co-cultures showed AHR-dependent regulation of immune-related genes, and scratch closure was also AHR-dependent.

Conclusion: The study demonstrates a context-dependent role of AHR in skin fibrosis and its interaction with TGFβ and Wnt/β-catenin signaling.

Keywords
Fibrosis ; Systemic sclerosis ; MMP1 ; Collagen type I ; Aryl hydrocarbon receptor.
Products