ArticleDevelopmental cell2021
VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Identification of Quality Markers in Viola kunawaresis Royel Using HPLC Fingerprints, Chemometric Analysis, and Network Pharmacology.Biomedical chromatography : BMC · 2026Article
- FGFR signaling establishes spatial gradients of secretory cell identities along the airway proximal-distal axis.Nature communications · 2026Article
- Article
- The SOX4-Semaphorin3C axis promotes esophageal adenocarcinoma progression.Cancer letters · 2025Article
- Fzd2 orchestrates canonical and non-canonical Wnt signaling to regulate lung development and fibrosis.Cell communication and signaling : CCS · 2025Article
- Article
- Article
- Cellular senescence-related gene signatures in idiopathic pulmonary fibrosis: insights from bioinformatics.Frontiers in immunology · 2025Article
- The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.European journal of immunology · 2025Article
- Hippo cooperates with p53 to regulate lung airway mucous cell metaplasia.Disease models & mechanisms · 2024Article
- Article
- The Modulation of Respiratory Epithelial Cell Differentiation by the Thickness of an Electrospun Poly-ε-Carprolactone Mesh Mimicking the Basement Membrane.International journal of molecular sciences · 2024Article
- The transcriptomic signature of respiratory sensitizers using an alveolar model.Cell biology and toxicology · 2024Article
- Article
- Single-cell analysis reveals alterations in cellular composition and cell-cell communication associated with airway inflammation and remodeling in asthma.Respiratory research · 2024Article
- In-silico identification and prioritization of therapeutic targets of asthma.Scientific reports · 2023Article
- Wilms Tumor 1-Driven Fibroblast Activation and Subpleural Thickening in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2023Review
- Contribution ofeLife · 2022Article
- Airway secretory cell fate conversion via YAP-mTORC1-dependent essential amino acid metabolism.The EMBO journal · 2022Article
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Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.
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