ArticleCardiovascular research2010
Fra-2 mediates oxygen-sensitive induction of transforming growth factor beta in cardiac fibroblasts.
Article in Cardiovascular research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Fra2, a potential therapeutic target for silicosis.Genes & diseases · 2026Article
- Cannabidiol Protects the Neonatal Mouse Heart from Hyperoxia-Induced Injury.International journal of molecular sciences · 2025Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia-Reperfusion Injury.Medicina (Kaunas, Lithuania) · 2025Article
- FOSL2 activates TGF-β1-mediated GLUT1/mTOR signaling to promote diabetic kidney disease.Journal of diabetes investigation · 2025Article
- Progress in the Study of Fra-2 in Respiratory Diseases.International journal of molecular sciences · 2024Review
- Role of Fra-2 in cancer.Cell death and differentiation · 2024Review
- FOSL2 deficiency delays nonalcoholic steatohepatitis progression by regulating LY6D-mediated NLRP3 activation.Human cell · 2022Article
- Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis, and reduces survival in a spontaneous xenograft model of human breast cancer.Journal of cancer research and clinical oncology · 2022Article
- The SUV4-20H Histone Methyltransferases in Health and Disease.International journal of molecular sciences · 2022Review
- Hub gene identification and prognostic model construction for isocitrate dehydrogenase mutation in glioma.Translational oncology · 2021Article
- Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer.Frontiers in oncology · 2021Article
- Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS.Nature communications · 2020Article
- Role of linc00174/miR-138-5p (miR-150-5p)/FOSL2 Feedback Loop on Regulating the Blood-Tumor Barrier Permeability.Molecular therapy. Nucleic acids · 2019Article
- MicroRNA (miR)-597-5p Inhibits Colon Cancer Cell Migration and Invasion by Targeting FOS-Like Antigen 2 (Frontiers in oncology · 2019Article
- TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging.Nature communications · 2018Article
- c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer.Oncology reports · 2017Article
- miR-597 inhibits breast cancer cell proliferation, migration and invasion through FOSL2.Oncology reports · 2017Article
- DNA methylation patterns associated with oxidative stress in an ageing population.BMC medical genomics · 2016Article
- Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimsIn the ischaemia-reperfused heart, transforming growth factor beta (TGFbeta) proteins trigger the differentiation of cardiac fibroblasts (CFs) contributing to fibrosis. Reoxygenation of the heart, in addition to being a trigger for reperfusion injury, induces tissue remodelling by hyperoxia-sensitive signalling processes involving TGFbeta. Here, we sought to characterize the molecular mechanisms responsible for the O(2)-sensitive transcriptional induction of TGFbeta in murine CF and to test the significance of such findings in the infarcted myocardium in vivo using laser capture microdissection. METHODS AND
resultsAll three isoforms of TGFbeta were induced in the CF-rich peri-infarct tissue as well as in CF exposed to hyperoxic challenge. Reporter studies demonstrated that TGFbeta transcription is hyperoxia inducible. Deletion of any one or both of the activating protein-1 (AP-1) binding sites in the TGFbeta reporter construct resulted in loss of O(2) sensitivity, demonstrating that AP-1 confers O(2) sensitivity to TGFbeta transcription. Fos-related AP-1 transcription factor (Fra-2) and Ask-1 (apoptosis signal-regulating kinase-1) were identified as key mediators of AP-1-dependent O(2)-sensitive TGFbeta transcription. Knockdown of Fra-2 significantly blunted O(2)-induced expression of TGFbeta1 as well as TGFbeta3 in CF. Knockdown of Ask-1 blunted hyperoxia-induced Fra-2 gene expression and nuclear localization in CF. Collectively, these observations point towards a central role of Ask-1 and Fra-2 in O(2)-inducible AP-1 activation and induction of TGFbeta.
conclusionTaken together with the observation that Fra-2-regulated genes are implicated in fibrosis, identification of Fra-2 as an O(2)-sensitive transcriptional regulator of inducible TGFbeta expression positions Fra-2 as an important player in reoxygenation-induced fibrosis.
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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.