ArticleCell death discovery2020
Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis.
Article in Cell death discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
The trial behind it
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
28 citing papers in PubMed, 40 citations in OpenAlex.
- Spatial transcriptomics unveils the in situ cellular and molecular hallmarks of the lung in fatal COVID-19.Nature communications · 2026Article
- Amniotic Mesenchymal Stromal Cell Administration Prevents and Stops Lung Fibrosis and Is Associated with Distinct Macrophage Signatures.Pharmaceutics · 2026Article
- Transcriptional and spatial profiling of fibroblasts from human lungs highlights CTHRC1+ cells as fibrogenic signaling hubs in fibrosis.bioRxiv : the preprint server for biology · 2026Article
- High-Altitude Hypoxic Preconditioning Attenuates Lipopolysaccharide-Induced Lung Injury and is Associated with Alveolar-Capillary Barrier Maintenance.Journal of inflammation research · 2026Article
- Microbiome-innate immune crosstalk in acute exacerbation of idiopathic pulmonary fibrosis: an amplification framework.Frontiers in immunology · 2026Review
- Decreased scleral Wnt5aNature communications · 2025Article
- Biomaterial-based 3D human lung models replicate pathological characteristics of early pulmonary fibrosis.Acta biomaterialia · 2025Article
- Spatial transcriptomics identifies SPARC as a prognostic marker in interstitial lung diseases.The Journal of pathology · 2025Article
- Epithelial damage and ageing: the perfect storm.Thorax · 2025Review
- Inhibition of DLK1 regulates AT2 differentiation and alleviates established pulmonary fibrosis by upregulating TTF-1/CLDN6.Respiratory research · 2025Article
- Airway basal stem cell-derived extracellular vesicles modulate proliferation, migration and collagen deposition of fibroblasts.Stem cell research & therapy · 2025Article
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Article
- Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways.Mucosal immunology · 2024Article
- Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.Cell reports. Medicine · 2024Article
- Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Highlighting fibroblast plasticity in lung fibrosis: the WI-38 cell line as a model for investigating the myofibroblast and lipofibroblast switch.Theranostics · 2024Article
- Role of mitochondria in inflammatory lung diseases.Frontiers in pharmacology · 2024Review
- Adipokines in pulmonary hypertension: angels or demons?Heliyon · 2023Review
- Lung extracellular matrix modulates KRT5Nature communications · 2023Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated in disease pathogenesis, however, the causes and mechanisms of the progressive fibrotic cascade are still poorly understood. As epithelial-mesenchymal interactions are essential for normal wound healing, through human 2D and 3D in vitro studies, we tested the hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media from IPFFs exaggerated the wound-healing response of primary human Type II alveolar epithelial cells (AECs). Furthermore, AECs co-cultured with IPFFs exhibited irregular epithelialization compared with those co-cultured with control fibroblasts (NHLFs) or AECs alone, suggesting that epithelial homeostasis is dysregulated in IPF as a consequence of the abnormal secretory phenotype of IPFFs. Secretome analysis of IPFF conditioned media and functional studies identified the matricellular protein, SPARC, as a key mediator in the epithelial-mesenchymal paracrine signaling, with increased secretion of SPARC by IPFFs promoting persistent activation of alveolar epithelium via an integrin/focal adhesion/cellular-junction axis resulting in disruption of epithelial barrier integrity and increased macromolecular permeability. These findings suggest that in IPF fibroblast paracrine signaling promotes persistent alveolar epithelial activation, so preventing normal epithelial repair responses and restoration of tissue homeostasis. Furthermore, they identify SPARC-mediated paracrine signaling as a potential therapeutic target to promote the restoration of lung epithelial homoestasis in IPF patients.
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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.