Activated Hedgehog signaling in keratocytes leads to stromal stiffness and impairs corneal regeneration.

ABSTRACT: The repair of corneal injuries remains a major challenge in clinical practice. Impaired corneal wound healing is closely associated with aberrantly activated stromal keratocytes and disorganized extracellular matrix. Here, we identify aberrant Hedgehog signaling in corneal keratocytes as a key driver of defective wound repair. In adult mice, Hedgehog signaling is suppressed in quiescent keratocytes but is pathologically reactivated following chemical injury, correlating with impaired repair. Keratocyte-specific Hedgehog activation via Ptch1 ablation disrupted corneal wound healing after epithelial scraping-a process that would normally resolve seamlessly under physiological conditions. Mechanistically, Hedgehog activation induced stromal thinning and stiffening through disorganized collage

SUBMITTER: Yu Q 

PROVIDER: S-EPMC12905386 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature