ArticleNature2015
Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 212 citations in OpenAlex.
- Hypoxia-inducible factor 1-alpha inhibition mitigates inflammatory responses induced by H9N2 avian influenza virus.Microbiology spectrum · 2026Article
- FGFR signaling establishes spatial gradients of secretory cell identities along the airway proximal-distal axis.Nature communications · 2026Article
- Elevation-associated shifts in plasma metabolite abundance and lung gene expression in the Xizang plateau frog, Nanorana parkeri.BMC genomics · 2026Article
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis.Nature communications · 2025Article
- Inhibition of Hedgehog signaling does not mitigate polycystic kidney disease severity in a Pkd1 mutant mouse model.Journal of cell science · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema.Science advances · 2025Article
- The sonic hedgehog signaling inhibitor cyclopamine improves pulmonary arterial hypertension via regulating the bone morphogenetic protein receptor 2 pathway.Scientific reports · 2025Article
- Deciphering the interplay: circulating cell-free DNA, signaling pathways, and disease progression in idiopathic pulmonary fibrosis.3 Biotech · 2025Review
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Article
- TGF-β1/SMAD3-mediated Non-canonical Hedgehog Signaling Promotes Pancreatic Stellate Cell Activation and Fibrosis in Chronic Pancreatitis.International journal of biological sciences · 2025Article
- Non-small cell lung cancer organoids: Advances and challenges in current applications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA.Nature communications · 2024Article
- A Residual N-Terminal Peptide Enhances Signaling of Depalmitoylated Hedgehog to the Patched Receptor.Journal of developmental biology · 2024Article
- NLRP3 inflammasome mediates abnormal epithelial regeneration and distal lung remodeling in silica‑induced lung fibrosis.International journal of molecular medicine · 2024Article
- Secretome of EMSCs neutralizes LPS‑induced acute lung injury via aerosol administration.International journal of molecular medicine · 2023Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Postnatal tissue quiescence is thought to be a default state in the absence of a proliferative stimulus such as injury. Although previous studies have demonstrated that certain embryonic developmental programs are reactivated aberrantly in adult organs to drive repair and regeneration, it is not well understood how quiescence is maintained in organs such as the lung, which displays a remarkably low level of cellular turnover. Here we demonstrate that quiescence in the adult lung is an actively maintained state and is regulated by hedgehog signalling. Epithelial-specific deletion of sonic hedgehog (Shh) during postnatal homeostasis in the murine lung results in a proliferative expansion of the adjacent lung mesenchyme. Hedgehog signalling is initially downregulated during the acute phase of epithelial injury as the mesenchyme proliferates in response, but returns to baseline during injury resolution as quiescence is restored. Activation of hedgehog during acute epithelial injury attenuates the proliferative expansion of the lung mesenchyme, whereas inactivation of hedgehog signalling prevents the restoration of quiescence during injury resolution. Finally, we show that hedgehog also regulates epithelial quiescence and regeneration in response to injury via a mesenchymal feedback mechanism. These results demonstrate that epithelial-mesenchymal interactions coordinated by hedgehog actively maintain postnatal tissue homeostasis, and deregulation of hedgehog during injury leads to aberrant repair and regeneration in the lung.
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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.