Hepatocyte Growth Factor Alleviates Dry Eye Disease by Modulating the HMGB1/TLR4 Signaling Pathway: Potential...

Dry eye disease (DED) is a prevalent ocular surface disorder involving persistent inflammatory responses, redox imbalance, and impairment of corneal epithelial integrity. Despite the recognized regenerative and immunomodulatory functions of hepatocyte growth factor (HGF), whether HGF contributes to the maintenance of ocular surface homeostasis during DED progression and the mechanisms involved remain largely undefined.

A hyperosmolar stress-induced HCEC injury model and a mouse model of experimental DED were established to evaluate the protective effects of HGF. Cell viability, inflammatory responses, oxidative stress, and apoptosis were assessed using CCK-8, ELISA, qRT-PCR, Western blotting, DCFH-DA staining, and flow cytometry. Corneal fluorescein staining and Schirmer tests were performed to evaluate ocular surface damage in mice. The involvement of the HMGB1/TLR4 pathway was investigated through molecular analyses and HMGB1 knockdown experiments.

HGF significantly alleviated hyperosmolarity-induced HCEC injury by enhancing cell viability, reducing ROS accumulation and apoptosis, and suppressing pro-inflammatory cytokine production. In DED mice, HGF treatment improved corneal epithelial defects, increased tear secretion, and reduced ocular surface inflammation. Mechanistically, HGF inhibited HMGB1/TLR4 signaling activation, while HMGB1 silencing mimicked the protective effects of HGF.

HGF protects against DED-associated corneal epithelial injury by suppressing HMGB1/TLR4-mediated inflammatory responses, suggesting its potential as a therapeutic target for DED.