ArticlePloS one2017
Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis.Nature biomedical engineering · 2026Article
- Natural therapeutics and traditional formulas targeting macrophage polarization in the fibrotic niche of idiopathic pulmonary fibrosis.Frontiers in immunology · 2026Review
- Article
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- Immunobiology of pulmonary fibrosis.Frontiers in immunology · 2025Review
- Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation.International journal of molecular sciences · 2024Article
- The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.Investigative ophthalmology & visual science · 2024Article
- Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.Nature biomedical engineering · 2023Article
- Monocytes and macrophages: emerging mechanisms and novel therapeutic targets in pulmonary fibrosis.American journal of physiology. Cell physiology · 2023Review
- Review
- Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.Respiratory research · 2023Article
- Article
- M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts.The Laryngoscope · 2021Article
- Immune dysregulation as a driver of idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2021Review
- An immune-related signature that to improve prognosis prediction of breast cancer.American journal of cancer research · 2021Article
- Comprehensive molecular characterization of circRNA-associated ceRNA network in constrictive pericarditis.Annals of translational medicine · 2020Article
- The pathogenesis and management of renal scarring in children with vesicoureteric reflux and pyelonephritis.Pediatric nephrology (Berlin, Germany) · 2020Review
- Injectable Gelatin Hydrogel Suppresses Inflammation and Enhances Functional Recovery in a Mouse Model of Intracerebral Hemorrhage.Frontiers in bioengineering and biotechnology · 2020Article
- Crystalline Silica Impairs Efferocytosis Abilities of Human and Mouse Macrophages: Implication for Silica-Associated Systemic Sclerosis.Frontiers in immunology · 2020Article
- Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis. Mice deficient in Rac2 were protected against bleomycin-induced fibrosis and displayed diminished collagen deposition in association with lower expression of alternatively activated profibrotic macrophage markers. We have demonstrated a macrophage autonomous process by which the injection of M2 and not M1 macrophages restored the bleomycin induced pulmonary fibrosis susceptibility in Rac2-/- mice, establishing a critical role for a macrophage Rac2 signaling axis in the regulation of macrophage differentiation and lung fibrosis in vivo. We also demonstrate that markers of alternative macrophage activation are increased in patients with IPF. Taken together, these studies define an important role for an integrin-driven Rac2 signaling axis in macrophages, and reveal that Rac2 activation is required for polarization of macrophages towards a profibrotic phenotype and progression of pulmonary fibrosis in vivo.
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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.