ArticleEBioMedicine2020
Airway epithelial cell differentiation relies on deficient Hedgehog signalling in COPD.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Respiratory mucosal immunity: Biological functions, diseases, prevention and therapy.Genes & diseases · 2026Review
- PHLDA1 knockdown exacerbates emphysema in COPD by attenuating proliferation of alveolar type II cells via modulating GLI1 nuclear translocation.Cellular and molecular life sciences : CMLS · 2026Article
- Catalpol inhibits Hedgehog signaling pathway to suppress proliferation and promote lipid accumulation in rat meibomian gland epithelial cells.Cytotechnology · 2025Article
- Multi-omics characterization of early chronic obstructive pulmonary disease.Respiratory research · 2025Article
- The Non-Antibacterial Effects of Azithromycin and Other Macrolides on the Bronchial Epithelial Barrier and Cellular Differentiation.International journal of molecular sciences · 2025Article
- Article
- POU5F1 bridges Hedgehog signaling and epithelial remodeling in COPD.Frontiers in cell and developmental biology · 2025Article
- Single-cell transcriptomics reveals e-cigarette vapor-induced airway epithelial remodeling and injury.Respiratory research · 2024Article
- Airway ciliated cells in adult lung homeostasis and COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Sonic Hedgehog Signaling Is Essential for Pulmonary Ionocyte Specification in Human and Ferret Airway Epithelia.American journal of respiratory cell and molecular biology · 2023Article
- Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis.Genes & diseases · 2023Review
- Arl13b controls basal cell stemness properties and Hedgehog signaling in the mouse epididymis.Cellular and molecular life sciences : CMLS · 2022Article
- Review
- Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis.International journal of molecular sciences · 2022Article
- An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea.Development (Cambridge, England) · 2022Article
- An innate contribution of human nicotinic receptor polymorphisms to COPD-like lesions.Nature communications · 2021Article
- Innate lymphoid cells are double-edged swords under the mucosal barrier.Journal of cellular and molecular medicine · 2021Review
- Impaired Ciliary Beat Frequency and Ciliogenesis Alteration during Airway Epithelial Cell Differentiation in COPD.Diagnostics (Basel, Switzerland) · 2021Article
- Primary ciliogenesis is a crucial step for multiciliated cell determinism in the respiratory epithelium.Journal of cellular and molecular medicine · 2021Article
- Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHedgehog (HH) pathway is constantly under scrutiny in the context of organ development. Lung morphogenesis requires HH signalling which participates thereafter to the pulmonary homeostasis by regulating epithelial cell quiescence and repair. Since epithelial remodelling is a hallmark of Chronic Obstructive Pulmonary Disease (COPD), we investigated whether the main molecular actors of HH pathway participate to airway epithelial cell differentiation and we analysed their alterations in COPD patients.
methodsSonic HH (Shh) secretion was assessed by ELISA in airway epithelial cell (AEC) air-liquid interface culture supernatants. HH pathway activation was evaluated by RT-qPCR, western blot and immunostaining. Inhibition of HH signalling was achieved upon Shh chelation during epithelial cell differentiation. HH pathway core components localization was investigated in lung tissues from non-COPD and COPD patients.
findingsWe demonstrate that progenitors of AEC produced Shh responsible for the activation of HH signalling during the process of differentiation. Preventing the ligand-induced HH activation led to the establishment of a remodelled epithelium with increased number of basal cells and reduced ciliogenesis. Gli2 activating transcription factor was demonstrated as a key-element in the regulation of AEC differentiation. More importantly, Gli2 and Smo were lost in AEC from COPD patients.
interpretationOur data suggest that HH pathway is crucial for airway epithelial cell differentiation and highlight its role in COPD-associated epithelial remodelling.
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Registered trials
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