ArticleNature medicine2016
Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers.
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Who cites it
208 citing papers in PubMed, 285 citations in OpenAlex.
- Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.Respiratory research · 2021Trial
- Comparative study on mouse models of acute exacerbation of pulmonary fibrosis.Experimental and therapeutic medicine · 2026Article
- Saving the lung from ozone pollutant: a new role of hyaluronan in alveolar regeneration.American journal of respiratory cell and molecular biology · 2026Article
- Activation of the impaired NAMPT/SIRT7/SOD2 axis restores alveolar progenitor cell renewal in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2026Article
- Hyaluronan Signaling Ameliorates the Epithelial Injury Response and Barrier Disruption After Ozone Exposure.Biomolecules · 2026Article
- Epithelial cells in chronic obstructive pulmonary disease exacerbations: Targets for lung repair.Pharmacological reviews · 2026Review
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Extracellular vesicles from alveolar macrophages promotes pulmonary fibrosis through suppression of lung alveolar regeneration.Journal of nanobiotechnology · 2026Article
- Hyaluronan of Different Molecular Weights Exerts Distinct Therapeutic Effects on Bleomycin-Induced Acute Respiratory Distress Syndrome.International journal of molecular sciences · 2026Article
- Hyaluronan Ameliorates Viral Pneumonia in Mice and Humans by Inhibiting Transcription Factor E2F1.American journal of respiratory cell and molecular biology · 2026Article
- ESRP1 drives epithelial-mesenchymal transition by activating EPAC-RAP1A signaling axis.Frontiers in medicine · 2026Article
- Multi-omics integration and machine learning reveal gut-immune signatures in idiopathic pulmonary fibrosis: insights from bulk RNA-seq, single-cell profiles, spatial transcriptomics, and experimental validation.Frontiers in immunology · 2026Article
- Genetic Strategies for Labeling AT2 Cells in Murine Lung via Abca3 and Etv5-Driven Reporters.Journal of respiratory biology and translational medicine · 2026Article
- High-throughput isolation of normal and pulmonary fibrosis human alveolar epithelial cells.Scientific reports · 2025Article
- Fzd2 orchestrates canonical and non-canonical Wnt signaling to regulate lung development and fibrosis.Cell communication and signaling : CCS · 2025Article
- The CCL20-integrin α5β1 interaction enhances TGF-β/Smad signaling to promote fibroblast activation in pulmonary fibrosis.Nature communications · 2025Article
- Evaluation of TAM Receptor Targeting in Pathophysiology of Idiopathic Pulmonary Fibrosis.Medicina (Kaunas, Lithuania) · 2025Article
- eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- STAT6 Activation Exacerbates Ferroptosis in Airway Epithelium by Inhibiting PRKN-Mediated Mitophagy in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
148 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Successful recovery from lung injury requires the repair and regeneration of alveolar epithelial cells to restore the integrity of gas-exchanging regions within the lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to the lung repair process. The mechanisms that regulate AEC2 renewal are incompletely understood. We provide evidence that expression of the innate immune receptor Toll-like receptor 4 (TLR4) and the extracellular matrix glycosaminoglycan hyaluronan (HA) on AEC2s are important for AEC2 renewal, repair of lung injury and limiting the extent of fibrosis. Either deletion of TLR4 or HA synthase 2 in surfactant-protein-C-positive AEC2s leads to impaired renewal capacity, severe fibrosis and mortality. Furthermore, AEC2s from patients with severe pulmonary fibrosis have reduced cell surface HA and impaired renewal capacity, suggesting that HA and TLR4 are key contributors to lung stem cell renewal and that severe pulmonary fibrosis is the result of distal epithelial stem cell failure.
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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.