Abstract

Hypertrophic scarring (HS) represents a proliferative disorder that emerges due to aberrant wound healing processes and is characterized by the excessive accumulation of extracellular matrix components. Recent research has highlighted the pivotal role of exosomes-nanoscale extracellular vesicles-as crucial mediators of intercellular communication in both tissue repair and pathological states. This study investigates the mechanism by which TGF-β1 modulates the cargo of keratinocyte-derived exosomes to promote the transfer of the long non-coding RNA linc01605. The results reveal that exosomes secreted by TGF-β1-stimulated keratinocytes exhibit heightened profibrotic activity. Upon internalization by human dermal fibroblasts (HDFs), these exosomes markedly enhance cellular proliferation, migration, and collagen I (COL1A1) expression. linc01605, encapsulated within these exosomes, has been identified as the primary molecular mediator. Mechanistically, linc01605 functions as a competitive endogenous RNA that binds miR-370-3p, thereby alleviating the repression of TGFBR2 expression and amplifying the canonical TGF-β1/Smads signaling pathway. In summary, this work elucidates a novel pathogenic pathway in which TGF-β1-induced keratinocyte-derived exosomes mediate the delivery of HS-associated linc01605 to drive fibrosis. These findings not only clarify a fundamental mechanism underlying HS pathogenesis but also reveal potential therapeutic targets for the development of innovative anti-fibrotic strategies.