EGFR-STAT1 pathway drives fibrosis initiation in fibroinflammatory skin diseases.

ABSTRACT: Chronic inflammatory skin diseases affect the health of millions of people worldwide, and those that feature fibrosis are refractory to treatments. The signals that determine whether fibrosis occurs during chronic skin inflammation are poorly understood. We generated a scRNA-seq atlas of seven inflammatory skin diseases and their healthy controls. Diseases with fibrosis demonstrate higher expression and activity of STAT1 in fibroblasts. Fibroblast STAT1 is required for skin fibrosis development in mice. STAT1 activation promotes a fibrotic gene expression profile which can be activated directly by EGFR in a JAK-independent manner and abrogated by genetic and pharmacologic STAT1 inhibition. The EGFR-STAT1 pathway is stimulated by high affinity EGFR ligands expressed by activated keratinocyt

SUBMITTER: Odell AV 

PROVIDER: S-EPMC12511620 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature