ArticleProceedings of the National Academy of Sciences of the United States of America2024
Pharmacological expansion of type 2 alveolar epithelial cells promotes regenerative lower airway repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Targeting Elastin-Derived Peptides Reverses Alveolar Epithelial Dysfunction in Chronic Obstructive Pulmonary Disease.MedComm · 2026Article
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Epithelial cells in chronic obstructive pulmonary disease exacerbations: Targets for lung repair.Pharmacological reviews · 2026Review
- Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial pyruvate metabolism in club cells drives airway inflammation.Stem cell reports · 2026Article
- High-Altitude Hypoxic Preconditioning Attenuates Lipopolysaccharide-Induced Lung Injury and is Associated with Alveolar-Capillary Barrier Maintenance.Journal of inflammation research · 2026Article
- Optimized protocol for processing murine tumor-bearing lung tissue for flow cytometry and single cell RNA-sequencing.bioRxiv : the preprint server for biology · 2025Article
- Review
- DPP4 inhibition curbs systemic inflammation.Critical care (London, England) · 2025Observational
- Novel Lung Cell-Penetrating Peptide Targets Alveolar Epithelial Type II Cells, Basal Cells, and Ionocytes.Pharmaceutics · 2025Article
- Epigenetic changes and serotype-specific responses of alveolar type II epithelial cells to Streptococcus pneumoniae in resolving influenza A virus infection.Cell communication and signaling : CCS · 2025Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to lower airway repair. Agents that promote the selective expansion of these cells might stimulate regeneration of the compromised alveolar epithelium, an etiology-defining event in several pulmonary diseases. From a high-content imaging screen of the drug repurposing library ReFRAME, we identified that dipeptidyl peptidase 4 (DPP4) inhibitors, widely used type 2 diabetes medications, selectively expand AEC2s and are broadly efficacious in several mouse models of lung damage. Mechanism of action studies revealed that the protease DPP4, in addition to processing incretin hormones, degrades IGF-1 and IL-6, essential regulators of AEC2 expansion whose levels are increased in the luminal compartment of the lung in response to drug treatment. To selectively target DPP4 in the lung with sufficient drug exposure, we developed NZ-97, a locally delivered, lung persistent DPP4 inhibitor that broadly promotes efficacy in mouse lung damage models with minimal peripheral exposure and good tolerability. This work reveals DPP4 as a central regulator of AEC2 expansion and affords a promising therapeutic approach to broadly stimulate regenerative repair in pulmonary disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.