ArticleThe American journal of pathology2015
Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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
33 citing papers in PubMed, 46 citations in OpenAlex.
- In-depth examination of the zinc-mitigation of the molecular effects of heat stress-induced intestinal damage in broilers.Poultry science · 2026Article
- Comprehensive insights into sepsis-induced cardiac dysfunction through proteomics and metabolomics.BMC research notes · 2026Article
- Ras-proximate-1 (RAP1): a prognosis and therapeutic target in the metastatic spread of breast cancer.Clinical & experimental metastasis · 2025Review
- Oxidative Stress and Inflammation-Related mRNAs Are Elevated in Serum of a Finnish Wet AMD Cohort.Investigative ophthalmology & visual science · 2024Article
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- PRMT5 is a therapeutic target in choroidal neovascularization.Scientific reports · 2023Article
- Rap1a Activity Elevated the Impact of Endogenous AGEs in Diabetic Collagen to Stimulate Increased Myofibroblast Transition and Oxidative Stress.International journal of molecular sciences · 2022Article
- Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022Article
- Review
- Review
- 7-ketocholesterol induces endothelial-mesenchymal transition and promotes fibrosis: implications in neovascular age-related macular degeneration and treatment.Angiogenesis · 2021Article
- Active Rap1-mediated inhibition of choroidal neovascularization requires interactions with IQGAP1 in choroidal endothelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Article
- Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities.Progress in retinal and eye research · 2021Review
- Article
- NADPH oxidase-induced oxidative stress in the eyes of hypertensive rats.Molecular vision · 2021Article
- IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation.Angiogenesis · 2020Article
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.International journal of retina and vitreous · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α-induced ROS generation. Apocynin reduced TNF-α-induced NF-κB and Rac1 activation, and inhibited TNF-α-induced CEC migration. TNF-α-induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α-induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2'-O-Me-cAMP prevented TNF-α-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α-induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process.
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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.