ArticleDevelopment (Cambridge, England)2010
Signaling via Alk5 controls the ontogeny of lung Clara cells.
Article in Development (Cambridge, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.Respiratory research · 2020Trial
- Concurrent jamming and mesenchymal-to-epithelial transitions during airway basal stem cell differentiation.iScience · 2026Article
- S100B triggers neuroendocrine macrophage networks to drive airway regeneration in mice.Nature communications · 2025Article
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- TGF-β controls alveolar type 1 epithelial cell plasticity and alveolar matrisome gene transcription in mice.The Journal of clinical investigation · 2024Article
- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
- Neonatal lung-derived SSEA-1iScience · 2022Article
- Activation of PI3K/p110α in the Lung Mesenchyme Affects Branching Morphogenesis and Club Cell Differentiation.Frontiers in cell and developmental biology · 2022Article
- Cellular and functional heterogeneity of the airway epithelium.Mucosal immunology · 2021Review
- Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells.Experimental and therapeutic medicine · 2021Article
- Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease.Disease models & mechanisms · 2020Review
- TGF-β Signaling in Lung Health and Disease.International journal of molecular sciences · 2018Review
- Spatial-Temporal Lineage Restrictions of Embryonic p63Developmental cell · 2018Article
- β-Catenin maintains lung epithelial progenitors after lung specification.Development (Cambridge, England) · 2018Article
- TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.Cold Spring Harbor perspectives in biology · 2018Review
- The role of TGFβ‑HGF‑Smad4 axis in regulating the proliferation of mouse airway progenitor cells.Molecular medicine reports · 2017Article
- A 3D epithelial-mesenchymal co-culture model of human bronchial tissue recapitulates multiple features of airway tissue remodeling by TGF-β1 treatment.Respiratory research · 2017Article
- Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Significance of Stat3 Signaling in Epithelial Cell Differentiation of Fetal Mouse Lungs.Acta histochemica et cytochemica · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Clara cells, together with ciliated and pulmonary neuroendocrine cells, make up the epithelium of the bronchioles along the conducting airways. Clara cells are also known as progenitor or stem cells during lung regeneration after injury. The mechanisms of Clara cell differentiation are largely unknown. Transforming growth factor beta (TGFbeta)is a multifunctional molecule with roles in normal development and disease pathogenesis. In this study, we deleted the TGFbeta type I receptor Alk5 in the embryonic lung epithelium using Gata5-Cre mice. Absence of Alk5 blocked Clara cell differentiation but had no effect on ciliated or pulmonary neuroendocrine cells. Hairy/Enhancer of Split-1, which is expressed in Clara cell putative ;progenitors' was found to be a downstream target of Alk5 in vivo and in vitro. Loss of Alk5-mediated signaling also stimulated Pten gene expression and inhibited ERK phosphorylation in vivo. Using lung epithelial cells, we show that Alk5-regulated Hes1 expression is stimulated through Pten and the MEK/ERK and PI3K/AKT pathways. Thus, the signaling pathway by which TGFbeta/ALK5 regulates Clara cell differentiation may entail inhibition of Pten expression, which in turn activates ERK and AKT phosphorylation.
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Registered trials
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.