LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF
Open accessAbstract
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.
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LTI-03 has been shown to exert strong antifibrotic and epithelial supportive effects in experimental animal models of lung fibrosis, in human IPF precision cut lung slices, and in human IPF alveolar organoids.
“LTI-03 has been shown to exert strong antifibrotic and epithelial supportive effects in experimental animal models of lung fibrosis15–17, in human IPF precision cut lung slices18, and in human IPF alveolar organoids19.”
From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [18]
The Results report that LTI-03 significantly reduced collagen staining in human IPF precision-cut lung slices, supporting the antifibrotic effect attributed to citation 18. The Discussion’s limitations section says the slices were largely devoid of viable type 1 and 2 epithelial cells and that analysis of epithelial-associated markers was limited; this paper therefore does not establish an epithelial-supportive effect in those slices. The animal-model and organoid claims carry other citations and are outside this verdict. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe CXCL7 results are consistent with prior data demonstrating decreased CXCL7 levels with LTI-03 treatment in IPF precision cut lung slice supernatants.
“These results are consistent with prior data demonstrating decreased CXCL7 levels with LTI-03 treatment in IPF PCLS supernatants18.”
From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [18]
The Results section reports that 10 μM LTI-03 suppressed many inflammatory and profibrotic mediators measured in IPF PCLS supernatants, and the Discussion identifies CXCL7 as a protein elevated in those cultures. Our copy does not specifically state that CXCL7 decreased with LTI-03 treatment; the Figure 3 caption also says no statistical tests were performed. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThese pharmacological effects were also demonstrated in IPF and donor precision cut lung slices, which contain all diseased lung cell types, as well as in both lung epithelial cell organoid cultures and fibroblasts sourced from end-stage IPF patients.
“These pharmacological effects were also demonstrated in IPF and donor precision cut lung slices (PCLS)18, which contain all diseased lung cell types, as well as in both lung epithelial cell organoid cultures19 and fibroblasts sourced from end-stage IPF patients20.”
From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [18]
The Introduction reports anti-fibrotic effects of LTI-03 in IPF precision-cut lung slices. The Discussion’s limitations section says comparison of pharmacological activity in donor slices was not performed; it also says the IPF explants were largely devoid of viable type 1 and 2 epithelial cells, so the claim that the slices contain all diseased lung cell types is overstated. The organoid and fibroblast claims carry separate citations and are not judged against this source. (LLM, conf=0.90)
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Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study
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“These phar-macologicaleffectswerealsodemonstratedinIPFanddonorprecision cut lung slices (PCLS) 18 , which contain all diseased lung cell types, as well as in both lung epithelial cell organoid cultures 19 and fi broblasts sourced from end-stage IPF patients 20 .”
Self-citationWang, D., Li, F., Chen, H., Deng, B., Cheng, L., Ma, J., Li, R., Qu, L., Xie, J., & Zhao, Y. (2026) · The FASEB Journal · doi:10.1096/fj.202504506r
- Authors
- 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.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Cedars-Sinai Medical Center (US)
- Vienna General Hospital (AT)
- Corresponding author
- MacKenzie, BreAnne
- Mahavadi, Poornima
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2025-09
- Volume
- 28
- Issue
- 9
- Pages
- 113437
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC12496166
- OpenAlex
- W4413682553
- Cited by
- 2
- References
- 42
- Citations by year
- 2026: 2
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart Lung and Blood Institute Division of Intramural Research
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- idiopathic pulmonary fibrosis, antifibrotic therapy, precision-cut lung slices, collagen deposition, profibrotic cytokines, PTEN signaling, PPAR signaling, nintedanib, apoptosis, ex vivo lung model
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