Silk Fibroin Peptides Promote Extracellular Matrix Homeostasis in Photoaging via Modulation of the ITGB1/FAK-TGF-β/Smad Signaling Axis

Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin β1 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-β (TGF-β)/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell–matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling.