Marine-derived surfactin derivatives suppress collagen production and interfere with the HSP47-collagen interaction in preclinical models.

Introduction: Pulmonary fibrosis is a chronic and relentlessly progressive interstitial lung disease characterized by irreversible scarring of the lung parenchyma, for which no curative therapies currently exist. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for proper collagen folding and secretion, has emerged as a compelling therapeutic target to mitigate pathological collagen deposition. Methods: To identify inhibitors of the HSP47-collagen interaction, we comprehensively screened a marine microorganism extract library. Initial screening revealed 16 extracts with inhibitory activity, and subsequent secondary screening narrowed these down to seven candidates. Among them, one extract exhibited potent, concentration-dependent inhibition of HSP47 activity and markedly suppressed collagen synthesis in lung fibroblasts at low concentrations. This lead extract was fractionated using high-performance liquid chromatography, and bioactive components were subsequently isolated. Results: Mass spectrometric analysis identified the active compounds as C14- and C15-surfactin, cyclic lipopeptides produced by Conclusion: Collectively, surfactin are novel inhibitors of the HSP47-collagen interaction with promising therapeutic potential for pulmonary fibrosis treatment.