ArticleScientific reports2021
Discovery of a new class of integrin antibodies for fibrosis.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 68 citations in OpenAlex.
- An inducible co-stimulator ligand (ICOSL)-based peptide therapy for proteinuric kidney diseases targeting αvβ3 integrin.Molecular biomedicine · 2026Article
- Targeting the remodeled peritoneal ecosystem: a paradigm shift from tumor cells to the microenvironment in gastric cancer peritoneal metastasis.Frontiers in immunology · 2026Review
- Mechanosensing Pathways in the Progression of Pulmonary Fibrosis.Current opinion in biomedical engineering · 2025Article
- Therapeutic Prospects of αv Integrins Inhibition in Fibrotic Lung Diseases and Carcinogenesis.International journal of molecular sciences · 2025Review
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- The immunoregulatory role of integrins in pulmonary diseases.Frontiers in immunology · 2025Review
- Si-ITGA6-Loaded Liposomes Inhibit Capsule Fibrosis via the FAK/PI3K/Akt Signaling Pathway in Adhesive Capsulitis of Shoulder.International journal of nanomedicine · 2025Article
- Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases.Frontiers in immunology · 2024Review
- Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option.Cells · 2022Review
- Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Article
- Thy-1 (CD90), Integrins and Syndecan 4 are Key Regulators of Skin Wound Healing.Frontiers in cell and developmental biology · 2022Review
- Emerging therapeutic opportunities for integrin inhibitors.Nature reviews. Drug discovery · 2022Review
- Therapeutic Approaches for Treating Pulmonary Arterial Hypertension by Correcting Imbalanced TGF-β Superfamily Signaling.Frontiers in medicine · 2021Review
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Authors and funding
28 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung fibrosis, or the scarring of the lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis is worse than most types of cancer. We previously discovered that MK-0429 is an equipotent pan-inhibitor of αv integrins that reduces proteinuria and kidney fibrosis in a preclinical model. In the present study, we further demonstrated that MK-0429 significantly inhibits fibrosis progression in a bleomycin-induced lung injury model. In search of newer integrin inhibitors for fibrosis, we characterized monoclonal antibodies discovered using Adimab's yeast display platform. We identified several potent neutralizing integrin antibodies with unique human and mouse cross-reactivity. Among these, Ab-31 blocked the binding of multiple αv integrins to their ligands with IC50s comparable to those of MK-0429. Furthermore, both MK-0429 and Ab-31 suppressed integrin-mediated cell adhesion and latent TGFβ activation. In IPF patient lung fibroblasts, TGFβ treatment induced profound αSMA expression in phenotypic imaging assays and Ab-31 demonstrated potent in vitro activity at inhibiting αSMA expression, suggesting that the integrin antibody is able to modulate TGFβ action though mechanisms beyond the inhibition of latent TGFβ activation. Together, our results highlight the potential to develop newer integrin therapeutics for the treatment of fibrotic lung diseases.
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