Fibrotic lung ECM upregulates SDC4/integrin-αvβ1 interaction and the interfering peptide SDC4_87-131 and its derivative peptides alleviate pulmonary fibrosis.

ABSTRACT: Fibroblast activation promotes remodeling of the extracellular matrix (ECM), and the fibrotic remodeling ECM further stimulating fibroblast activation and advancing pulmonary fibrosis (PF). syndecan-4 (SDC4) is the key mediator of ECM-cell signaling, but its action in PF remains unclear. Using decellularized lung ECM (dECM), this study found that fibrotic ECM enhanced fibroblast activation via SDC4-regulated integrin-αvβ1 expression and activation, and FAK/AKT phosphorylation. Meanwhile, SDC4 knockdown inhibited fibrotic ECM-induced TGF-β1 synthesis and PKCα activation. A Duolink-proximity ligation assay confirmed extracellular interactions between SDC4 and integrin-αvβ1, and the SDC4 blocking antibody Anti-SDC4_(93-121) prevented this interaction, resulting in an effect consiste

SUBMITTER: Zhu L 

PROVIDER: S-EPMC12313019 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature