ArticleThe Journal of clinical investigation2019
Fra-2-expressing macrophages promote lung fibrosis in mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 111 citations in OpenAlex.
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Extracellular matrix phenotyping by imaging mass cytometry defines distinct cellular matrix environments associated with allergic airway inflammation.Molecular systems biology · 2026Article
- Fosl2 Regulates FSH-Dependent Follicle Maturation Through Feedback Amplification of FSH/FSHR Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the Fra2/LCN2 axis attenuates PMRedox biology · 2026Article
- Immunomodulation by collagen VI across fibrotic and tumor microenvironmental contexts.Histology and histopathology · 2026Review
- Identification of an immediate-early gene-activated fibroblast state in frozen shoulder capsular fibrosis.iScience · 2026Article
- Pulmonary fibrosis: Emerging targets and novel therapeutics.The Journal of international medical research · 2026Review
- FOSL2 regulates endothelial cell state and chromatin accessibility in systemic sclerosis pulmonary vascular remodeling.JCI insight · 2026Article
- Profibrotic macrophage populations and cell communications in pulmonary fibrosis.Journal of physiology and biochemistry · 2026Review
- Mechanical gating of tendon fibrogenic transcription in systemic sclerosis.Nature communications · 2026Article
- Fra2, a potential therapeutic target for silicosis.Genes & diseases · 2026Article
- Continuous antiretroviral therapy induces progressive senescence-like reprogramming of alveolar macrophages.Frontiers in immunology · 2026Article
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- FAPI TracerPharmaceuticals (Basel, Switzerland) · 2025Article
- The spatial and temporal activation of macrophages during fibrosis.Nature reviews. Immunology · 2025Review
- SESN3 restrains the progress of idiopathic pulmonary fibrosis by targeting the activity of FOSL2.Biology direct · 2025Article
- Circ-myh8/KAT7 Affects PANoptosis in Pulmonary Arterial Smooth Muscle Cells: Involvement of Super-Enhancers in FOSL2 Expression.Journal of the American Heart Association · 2025Article
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Scutellarin prevents obesity-induced renal fibrosis via reduced activation of AP-1.Journal of translational medicine · 2025Article
- Integrated bioinformatics analysis screened the key genes and pathways of idiopathic pulmonary fibrosis.Scientific reports · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 9 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a deadly disease with limited therapies. Tissue fibrosis is associated with Type 2 immune response, although the causal contribution of immune cells is not defined. The AP-1 transcription factor Fra-2 is upregulated in IPF lung sections and Fra-2 transgenic mice (Fra-2tg) exhibit spontaneous lung fibrosis. Here we show that Bleomycin-induced lung fibrosis is attenuated upon myeloid-inactivation of Fra-2 and aggravated in Fra-2tg bone marrow chimeras. Type VI collagen (ColVI), a Fra-2 transcriptional target, is up-regulated in three lung fibrosis models, and macrophages promote myofibroblast activation in vitro in a ColVI- and Fra-2-dependent manner. Fra-2 or ColVI inactivation does not affect macrophage recruitment and alternative activation, suggesting that Fra-2/ColVI specifically controls the paracrine pro-fibrotic activity of macrophages. Importantly, ColVI knock-out mice (KO) and ColVI-KO bone marrow chimeras are protected from Bleomycin-induced lung fibrosis. Therapeutic administration of a Fra-2/AP-1 inhibitor reduces ColVI expression and ameliorates fibrosis in Fra-2tg mice and in the Bleomycin model. Finally, Fra-2 and ColVI positively correlate in IPF patient samples and co-localize in lung macrophages. Therefore, the Fra-2/ColVI pro-fibrotic axis is a promising biomarker and therapeutic target for lung fibrosis, and possibly other fibrotic diseases.
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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.