ArticleAmerican journal of respiratory and critical care medicine2006
Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum.
Article in American journal of respiratory and critical care medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed.
- Non-Resolving Repair in Idiopathic Pulmonary Fibrosis: From Failed Cellular Transitions to Architectural Lock-In.International journal of molecular sciences · 2026Review
- The pleuroparenchymal fibroelastosis atlas reveals aberrant cell states and their zonation as an alternate roadmap to lung fibrosis.Science advances · 2026Article
- Mechanisms on How Matricellular Microenvironments Sustain Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Acute Exacerbation of Idiopathic Pulmonary Fibrosis in the Setting of Acute Eosinophilic Pneumonia.HCA healthcare journal of medicine · 2025Review
- Citrullinated and malondialdehyde-acetaldehyde-modified fibrinogen activates macrophages and promotes profibrotic responses in human lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- Proteolysis and Contractility Regulate Tissue Opening and Wound Healing by Lung Fibroblasts in 3D Microenvironments.Advanced healthcare materials · 2024Article
- Thin-Section CT in the Categorization and Management of Pulmonary Fibrosis including Recently Defined Progressive Pulmonary Fibrosis.Radiology. Cardiothoracic imaging · 2024Review
- The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Sustainably released nanoparticle-based rhynchophylline limits pulmonary fibrosis by inhibiting the TEK-PI3K/AKT signaling pathway.Translational lung cancer research · 2023Article
- A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression.International journal of molecular sciences · 2023Review
- Tensions in Taxonomies: Current Understanding and Future Directions in the Pathobiologic Basis and Treatment of Group 1 and Group 3 Pulmonary Hypertension.Comprehensive Physiology · 2023Review
- The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.JCI insight · 2022Article
- Biomechanical Force and Cellular Stiffness in Lung Fibrosis.The American journal of pathology · 2022Review
- Immunofluorescence-guided segmentation of three-dimensional features in micro-computed tomography datasets of human lung tissue.Royal Society open science · 2021Article
- Hypoxia in Cancer and Fibrosis: Part of the Problem and Part of the Solution.International journal of molecular sciences · 2021Review
- Stereology as the 3D tool to quantitate lung architecture.Histochemistry and cell biology · 2021Review
- Co-delivery of siPTPN13 and siNOX4Theranostics · 2021Article
- Review
33 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
backgroundUsual interstitial pneumonia (UIP), the pathologic correlate of idiopathic pulmonary fibrosis, contains characteristic discrete areas of fibroblasts, myofibroblasts, and newly formed collagen, termed "fibroblast foci." These lesions are argued to represent isolated sites of recurrent acute lung injury and suggested to be the mechanism of disease progression. We hypothesized that, rather than isolated, these lesions are part of an organized neoplasm.
methodsMorphometric analysis of pentachrome-stained histologic sections of UIP was performed. Using point-counting technique on serial sections, fibroblast foci, arteries, and macrophage clusters were identified and we determined their individual "connectiveness" by estimating the Euler number. Two-dimensional micrographs were collated into a three-dimensional array from which a visual three-dimensional reconstruction could be constructed. Clonality analysis was performed using human androgen receptor gene methylation assay.
resultsBlood vessels show significant connectivity with a Euler number of 2, whereas macrophage clusters exhibited no connectivity. The fibroblast foci showed a high level of interconnection with Euler numbers ranging from 19 to 39. The computer generated three-dimensional models provide a visual confirmation of this connectiveness. Human androgen receptor gene methylation assay analysis of the foci showed balanced methylation consistent with polyclonality.
conclusionsThe fibroblast foci of UIP are the leading edge of a complex reticulum that is highly interconnected and extends from the pleura into the underlying parenchyma. It is a reactive, rather than a malignant, process.
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