ArticleInternational journal of molecular sciences2022
Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Network-based single-cell analysis identifies a proliferative GZMBJournal of translational medicine · 2026Article
- MicroRNA-regulated signaling and tumor microenvironment modulation in lung cancer: mechanistic insights and translational opportunities.Cancer cell international · 2026Review
- Elevated Senescence Markers in Developing Trisomy 21 Human Lungs.American journal of respiratory cell and molecular biology · 2025Article
- Morphological and molecular aspects of lung development.Histology and histopathology · 2025Review
- Origin and stepwise evolution of vertebrate lungs.Nature ecology & evolution · 2025Article
- Article
- POU5F1 bridges Hedgehog signaling and epithelial remodeling in COPD.Frontiers in cell and developmental biology · 2025Article
- Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.American journal of respiratory and critical care medicine · 2024Article
- Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants.American journal of human genetics · 2024Article
- P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.Leukemia · 2024Article
- NLRP3 inflammasome mediates abnormal epithelial regeneration and distal lung remodeling in silica‑induced lung fibrosis.International journal of molecular medicine · 2024Article
- Development and Disorders of the Airway in Bronchopulmonary Dysplasia.Children (Basel, Switzerland) · 2023Review
- Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients.American journal of respiratory and critical care medicine · 2023Article
- Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome.Cellular and molecular life sciences : CMLS · 2023Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The Hedgehog (HH) signaling pathway plays an essential role in mouse lung development. We hypothesize that the HH pathway is necessary for branching during human lung development and is impaired in pulmonary hypoplasia. Single-cell, bulk RNA-sequencing data, and human fetal lung tissues were analyzed to determine the spatiotemporal localization of HH pathway actors. Distal human lung segments were cultured in an air-liquid interface and treated with an SHH inhibitor (5E1) to determine the effect of HH inhibition on human lung branching, epithelial-mesenchymal markers, and associated signaling pathways in vitro. Our results showed an early and regulated expression of HH pathway components during human lung development. Inhibiting HH signaling caused a reduction in branching during development and dysregulated epithelial (SOX2, SOX9) and mesenchymal (ACTA2) progenitor markers. FGF and Wnt pathways were also disrupted upon HH inhibition. Finally, we demonstrated that HH signaling elements were downregulated in lung tissues of patients with a congenital diaphragmatic hernia (CDH). In this study, we show for the first time that HH signaling inhibition alters important genes and proteins required for proper branching of the human developing lung. Understanding the role of the HH pathway on human lung development could lead to the identification of novel therapeutic targets for childhood pulmonary diseases.
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Registered trials
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