LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF

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, <i>ex vivo</i> 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.

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Publication Details

Journal
iScience
Published
2025-08-26
DOI
https://doi.org/10.1016/j.isci.2025.113437
Citations
2
Primary Topic
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Type
article
Field-Weighted Citation Impact
3.04
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article

LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF

Milena S. Espíndola, Yago Amigo Pinho Jannini de Sá, Brian Windsor, Clemens Ruppert et al.
2 citations
iScience
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
3.04
article

LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF

Milena S. Espíndola, Yago Amigo Pinho Jannini de Sá, Brian Windsor, Clemens Ruppert, Ana Lúcia Coelho, Poornima Mahavadi, Brecht Creyns, Cory M. Hogaboam, Clemens Aigner, BreAnne MacKenzie, Andreas Güenther
article en
2 citations

Abstract

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, <i>ex vivo</i> 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.

iScienceVol. 28(9)
Cedars-Sinai Medical Center (US), Vienna General Hospital (AT), Universities of Giessen and Marburg Lung Center (DE), Io Therapeutics (United States) (US), Cardio-Pulmonary Institute (DE)
Openalex Percentile: Top 8%
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
3.04
DOIOpen Access PDFOpenAlex
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