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 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.