ArticleJournal of cellular and molecular medicine2021
The HIF-1α/p53/miRNA-34a/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Histone deacetylase 3‑mediated histone deacetylation combined with activating transcription factor 3 promotes renal fibrosis by inhibiting Klotho.Molecular medicine reports · 2026Article
- Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex.Experimental eye research · 2026Review
- Uremic toxin p‑cresyl sulfate enhances the calcification of aortic valvular interstitial cells via klotho/sirtuin‑1 signaling.Molecular medicine reports · 2026Article
- Key role of transcription factors network in proliferative vitreoretinal diseases development.Cell & bioscience · 2026Review
- Serum Klotho Levels and Major Age-Related Ocular Disorders: A Cross-Sectional and Genetic Association Study.Translational vision science & technology · 2026Article
- Stage-associated immunoproteomic profiling of serum autoantibody-captured retinal antigens in age-related macular degeneration.Frontiers in immunology · 2026Article
- Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.Biomolecules · 2025Review
- Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.International journal of molecular medicine · 2025Article
- Hypoxia and growth factor profiling in high myopia: linking HIF-1α suppression and PDGF-BB activation to structural degeneration.Frontiers in medicine · 2025Article
- Article
- Oxidative Stress and Inflammation-Related mRNAs Are Elevated in Serum of a Finnish Wet AMD Cohort.Investigative ophthalmology & visual science · 2024Article
- α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.Cell communication and signaling : CCS · 2024Article
- Recent Insights into Roles of Hypoxia-Inducible Factors in Retinal Diseases.International journal of molecular sciences · 2024Review
- Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction.Endocrine reviews · 2024Review
- Intertwined regulators: hypoxia pathway proteins, microRNAs, and phosphodiesterases in the control of steroidogenesis.Pflugers Archiv : European journal of physiology · 2024Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma.Oncology letters · 2023Article
- Klotho: A new therapeutic target in diabetic retinopathy?World journal of diabetes · 2023Review
- RO4929097, a Selective γ-Secretase Inhibitor, Inhibits Subretinal Fibrosis Via Suppressing Notch and ERK1/2 Signaling in Laser-Induced Mouse Model.Investigative ophthalmology & visual science · 2022Article
- Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans.EBioMedicine · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti-vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) increases the stability and activation of p53, which activates microRNA-34a (miRNA-34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA-34a that inhibits fibrosis. This study aimed to explore the role of the HIF-1α/p53/miRNA-34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia-induced HIF-1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE-19 cells (a human RPE cell line). HIF-1α-dependent p53 activation up-regulated miRNA-34a expression in ARPE-19 cells following hypoxia. Moreover, hypoxia-induced p53-dependent miRNA-34a inhibited the expression of Klotho in ARPE-19 cells. Additionally, the HIF-1α/p53/miRNA-34a/Klotho axis facilitated hypoxia-induced EMT in ARPE-19 cells. In vivo, blockade of the HIF-1α/p53/miRNA-34a/Klotho axis alleviated the formation of mouse laser-induced CNV and subretinal fibrosis. In short, the HIF-1α/p53/miRNA-34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.
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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.