597 Altered mechano-sensing and autophagy in keloid dermal fibroblasts

Keloid scars, which are excessive forms of cutaneous scarring, overgrow the boundaries original wound and do not regress spontaneously. Although keloid pathogenesis has been linked to numerous dysregulated signalling pathways, underlying causes remain poorly understood. scars have shown be 10-50 times stiffer than normal skin often form in areas body where tension is high. As a result, it thought that formation may influenced by mechanical forces. The aim this study was investigate direct effects tissue stiffness on behaviour (NDF) dermal fibroblasts (KDF) explore potential crosstalk with pathways. To response extracellular matrix (ECM) both NDFs KDFs were cultured collagen-coated polyacrylamide (PA) hydrogels mimicking (8kPa) (70-214kPa). became more spread stiff substrates compared soft increased focal adhesions F-actin stress fibres, changes observed within NDFs. Pathway analysis RNA-sequencing data identified autophagy as mechanosensitive pathway KDFs. Follow-up investigations showed LC3-II (a key regulator) protein levels when grown PA soft. Additionally, preliminary experiments indicated autophagic flux intact but impaired KDFs, sensitive treatment myosin-II inhibitor, blebbistatin, demonstrating importance process autophagy. In conclusion, project mechano-responsive ECM mechanically altered These findings revealed novel biomechanical-autophagy axis contribute on-going studies elucidate functional role mechanism deposition scar formation.