ArticleThe Biochemical journal2009
Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger.
Article in The Biochemical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- Iron: More than Meets the Eye.Nutrients · 2025Review
- Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver.Cells · 2024Article
- Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis.International journal of molecular sciences · 2023Review
- Low ceruloplasmin levels exacerbate retinal degeneration in a hereditary hemochromatosis model.Disease models & mechanisms · 2023Article
- Pseudovitelliform maculopathy associated with hereditary hemochromatosis.Medical hypothesis, discovery & innovation ophthalmology journal · 2023Article
- Protrusion of KCNJ13 Gene Knockout Retinal Pigment Epithelium Due to Oxidative Stress-Induced Cell Death.Investigative ophthalmology & visual science · 2022Article
- Expression patterns of iron regulatory proteins after intense light exposure in a cone-dominated retina.Molecular and cellular biochemistry · 2021Article
- Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration.Aging and disease · 2021Review
- Effects of Excess Iron on the Retina: Insights From Clinical Cases and Animal Models of Iron Disorders.Frontiers in neuroscience · 2021Review
- Selenomethionine (Se-Met) Induces the Cystine/Glutamate Exchanger SLC7A11 in Cultured Human Retinal Pigment Epithelial (RPE) Cells: Implications for Antioxidant Therapy in Aging Retina.Antioxidants (Basel, Switzerland) · 2020Article
- Review
- Chronic exposure to excess iron promotes EMT and cancer via p53 loss in pancreatic cancer.Asian journal of pharmaceutical sciences · 2020Article
- Fenofibrate prevents iron induced activation of canonical Wnt/β-catenin and oxidative stress signaling in the retina.NPJ aging and mechanisms of disease · 2020Article
- Identification, Expression, and Roles of the Cystine/Glutamate Antiporter in Ocular Tissues.Oxidative medicine and cellular longevity · 2020Review
- Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration.The American journal of pathology · 2019Article
- Environmental stress impairs photoreceptor outer segment (POS) phagocytosis and degradation and induces autofluorescent material accumulation in hiPSC-RPE cells.Cell death discovery · 2019Article
- Potential Treatment of Retinal Diseases with Iron Chelators.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.Scientific reports · 2018Article
- Article
- Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.Investigative ophthalmology & visual science · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Haemochromatosis is an iron-overload disorder with age-dependent oxidative stress and dysfunction in a variety of tissues. Mutations in HFE (histocompatability leucocyte antigen class I-like protein involved in iron homoeostasis) are responsible for most cases of haemochromatosis. We demonstrated recently that HFE is expressed exclusively in the basal membrane of RPE (retinal pigment epithelium). In the present study, we used Hfe-/- mice to examine ferritin levels (an indirect readout for iron levels) and morphological changes in retina. We found increased ferritin accumulation in retina in 18-month-old, but not in 2-month-old, mice with considerable morphological damage compared with age-matched controls. The retinal phenotype included hypertrophy and hyperplasia of RPE. RPE cells isolated from Hfe-/- mice exhibited a hyperproliferative phenotype. We also compared the gene expression profile between wild-type and Hfe-/- RPE cells by microarray analysis. These studies showed that many cell cycle-related genes were differentially regulated in Hfe-/- RPE cells. One of the genes up-regulated in Hfe-/- RPE cells was Slc7a11 (where Slc is solute carrier) which codes for the 'transporter proper' xCT in the heterodimeric cystine/glutamate exchanger (xCT/4F2hc). This transporter plays a critical role in cellular glutathione status and cell-cycle progression. We confirmed the microarrray data by monitoring xCT mRNA levels by RT (reverse transcription)-PCR and also by measuring transport function. We also found increased levels of glutathione and the transcription factor/cell-cycle promoter AP1 (activator protein 1) in Hfe-/- RPE cells. Wild-type mouse RPE cells and human RPE cell lines, when loaded with iron by exposure to ferric ammonium citrate, showed increased expression and activity of xCT, reproducing the biochemical phenotype observed with Hfe-/- RPE cells.
Indexed as
Identifiers
What OpenQuestion holds
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.