Idiopathic pulmonary fibrosis (IPF) features excessive extracellular matrix deposition driven by activated fibroblasts and dysregulated signaling pathways. To assess the anti-fibrotic effects of LTI-03, a caveolin-1 scaffolding domain peptide, ex vivo precision-cut lung slices (PCLS) from patients with IPF were evaluated using bulk RNA sequencing, Ingenuity Pathway Analysis, and immunofluorescence. LTI-03 dose-dependently reduced collagen protein levels, suppressed pro-fibrotic cytokines, inhibited pro-fibrotic pathways, and activated protective mechanisms such as PTEN and PPAR signaling. Modulation was comparable to nintedanib but without the induction of apoptosis or necrosis pathways. These results demonstrate LTI-03's potential therapeutic efficacy in a highly relevant translational disease model and support LTI-03 as a promising next-generation therapeutic to halt IPF progression and improve patient outcomes.
- MacKenzie, B.
- Mahavadi, P.
- Pinho Jannini-Sa, Y. A.
- Creyns, B.
- Coelho, A. L.
- Espindola, M.
- Ruppert, C.
- Windsor, B.
- Aigner, C.
- Hogaboam, C. M.
- Guenther, A.
Keywords
- pharmacology
- transcriptomics
