ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Orphan nuclear receptor TR3/Nur77 improves wound healing by upregulating the expression of integrin β4.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. 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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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Transcription Factor Activity Regulating Macrophage Heterogeneity during Skin Wound Healing.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- Nur77 Mediates Anaphylaxis by Regulating miR-21a.Current issues in molecular biology · 2024Article
- Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.Theranostics · 2024Article
- Article
- PSKH1 affects proliferation and invasion of osteosarcoma cells via the p38/MAPK signaling pathway.Oncology letters · 2023Article
- NR4A1-3 nuclear receptor activity and immune cell dysregulation in rheumatic diseases.Frontiers in medicine · 2022Review
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial-mesenchymal transition of hepatic stellate cells.Open medicine (Warsaw, Poland) · 2021Article
- Biliary damage and liver fibrosis are ameliorated in a novel mouse model lacking l-histidine decarboxylase/histamine signaling.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Identification of Genetic Biomarkers for Diagnosis of Myocardial Infarction Compared with Angina Patients.Cardiovascular therapeutics · 2020Article
- Pre-mRNA Processing Factor 8 Accelerates the Progression of Hepatocellular Carcinoma by Regulating the PI3K/Akt Pathway.OncoTargets and therapy · 2020Article
- TAFA5 promotes proliferation and migration in gastric cancer.Molecular medicine reports · 2019Article
- Overexpression of carboxypeptidase X M14 family member 2 predicts an unfavorable prognosis and promotes proliferation and migration of osteosarcoma.Diagnostic pathology · 2019Article
- Overexpression of CPXM2 predicts an unfavorable prognosis and promotes the proliferation and migration of gastric cancer.Oncology reports · 2019Article
- DLL4 and Jagged1 are angiogenic targets of orphan nuclear receptor TR3/Nur77.Microvascular research · 2019Article
- Orphan nuclear receptor TR3/Nur77 differentially regulates the expression of integrins in angiogenesis.Microvascular research · 2019Article
- The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma.Cancer management and research · 2019Article
- Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity.The Journal of clinical investigation · 2018Article
- The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis.Oncotarget · 2017Review
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Tissue repair/wound healing, in which angiogenesis plays an important role, is a critical step in many diseases including chronic wound, myocardial infarction, stroke, cancer, and inflammation. Recently, we were the first to report that orphan nuclear receptor TR3/Nur77 is a critical mediator of angiogenesis and its associated microvessel permeability. Tumor growth and angiogenesis induced by VEGF-A, histamine, and serotonin are almost completely inhibited in Nur77 knockout mice. However, it is not known whether TR3/Nur77 plays any roles in wound healing. In these studies, skin wound-healing assay was performed in 3 types of genetically modified mice having various Nur77 activities. We found that ectopic induction of Nur77 in endothelial cells of mice is sufficient to improve skin wound healing. Although skin wound healing in Nur77 knockout mice is comparable to the wild-type control mice, the process is significantly delayed in the EC-Nur77-DN mice, in which a dominant negative Nur77 mutant is inducibly and specifically expressed in mouse endothelial cells. By a loss-of-function assay, we elucidate a novel feed-forward signaling pathway, integrin β4 → PI3K → Akt → FAK, by which TR3 mediates HUVEC migration. Furthermore, TR3/Nur77 regulates the expression of integrin β4 by targeting its promoter activity. In conclusion, expression of TR3/Nur77 improves wound healing by targeting integrin β4. TR3/Nur77 is a potential candidate for proangiogenic therapy. The results further suggest that TR3/Nur77 is required for pathologic angiogenesis but not for developmental/physiologic angiogenesis and that Nur77 and its family members play a redundant role in normal skin wound healing.
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