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 Bacillus subtilis . Treatment with surfactin significantly attenuated collagen production in pulmonary fibroblasts without altering HSP47 expression, suggesting inhibition through disruption of the HSP47–collagen interaction. Furthermore, oral administration of surfactin markedly reduced lung hydroxyproline content, demonstrating substantial antifibrotic efficacy in vivo . Conclusion Collectively, surfactin are novel inhibitors of the HSP47–collagen interaction with promising therapeutic potential for pulmonary fibrosis treatment.
Okuno et al. (Tue,) studied this question.