Lamellarin D Acts as an Inhibitor of Type I Collagen Production.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease characterized by irreversible loss of lung function and a poor prognosis. Type I collagen, a major component of the extracellular matrix, plays a central role in the pathogenesis of fibrosis and is considered a key molecular target for therapeutic intervention. While current anti-fibrotic therapies demonstrate limited efficacy in slowing disease progression, their clinical impact remains suboptimal due to poor pharmacokinetic properties and non-curative therapy. Moreover, the development of effective anti-fibrotic agents targeting collagen synthesis is hindered by the absence of robust, cost-effective, high-throughput drug screening platforms. In this study, we established a novel screening system designed to identify small molecules that inhibit the expression of the COL1A2 gene, which encodes type I collagen. Utilizing this system, we screened a library of natural and synthetic compounds developed at Nagasaki University and identified lamellarin D as a potent inhibitor of COL1A2 expression and subsequent type I collagen production. These findings suggest that lamellarin D, through its unique molecular mechanism, may serve as the foundation for the development of a new class of IPF treatments aimed at targeting the underlying fibrotic processes.