ArticleCell death & disease2014
Dysfunction of the stress-responsive FOXC1 transcription factor contributes to the earlier-onset glaucoma observed in Axenfeld-Rieger syndrome patients.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.Nature genetics · 2016Pooled it
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- Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma.International journal of molecular sciences · 2024Article
- Transcription factor roles in the local adaptation to temperature in the Andean Spiny Toad Rhinella spinulosa.Scientific reports · 2024Article
- Glaucoma Animal Models beyond Chronic IOP Increase.International journal of molecular sciences · 2024Review
- A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injuryActa pharmaceutica Sinica. B · 2021Article
- FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Article
- The Transcription Factor Foxc1 Promotes Osteogenesis by Directly Regulating Runx2 in Response of Intermittent Parathyroid Hormone (1-34) Treatment.Frontiers in pharmacology · 2020Article
- Analysis of variants in Chinese individuals with primary open-angle glaucoma using molecular inversion probe (MIP)-based panel sequencing.Molecular vision · 2020Article
- Forkhead box C1 promotes metastasis and invasion of non-small cell lung cancer by binding directly to the lysyl oxidase promoter.Cancer science · 2019Article
- Differential Glycosylation and Modulation of Camel and Human HSP Isoforms in Response to Thermal and Hypoxic Stresses.International journal of molecular sciences · 2018Article
- α7 nicotinic acetylcholine receptor signaling modulates the inflammatory phenotype of fetal brain microglia: first evidence of interference by iron homeostasis.Scientific reports · 2017Article
- Inhibition of Rho Kinase Induces Antioxidative Molecules and Suppresses Reactive Oxidative Species in Trabecular Meshwork Cells.Journal of ophthalmology · 2017Article
- A Novel Mutation inFrontiers in cardiovascular medicine · 2017Article
- Sixteen kiwi (Apteryx spp) transcriptomes provide a wealth of genetic markers and insight into sex chromosome evolution in birds.BMC genomics · 2016Article
- Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation.International journal of biological sciences · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the Forkhead Box C1 (FOXC1) transcription factor gene are associated with Axenfeld-Rieger syndrome (ARS), a developmental disorder affecting structures in the anterior segment of the eye. Approximately 75% of ARS patients with FOXC1 mutations develop earlier-onset glaucoma. Constant exposure of the trabecular meshwork (TM), located in the anterior segment of the eye, to oxidative stress is predicted to be a risk factor for developing glaucoma. Stress-induced death of TM cells results in dysfunction of the TM, leading to elevated intraocular pressure, which is a major risk factor for developing glaucoma. FOXC1 is predicted to maintain homeostasis in TM cells by regulating genes that are important for stress response. In this study, we show that a member of the heat-shock 70 family of proteins, HSPA6, is a target gene of FOXC1. HSPA6 protein, which is only induced under severe oxidative stress conditions, has a protective function in human trabecular meshwork (HTM) cells. We also show that FOXC1 is anti-apoptotic as knocking down FOXC1 significantly decreases HTM cell viability. In addition, we show that FOXC1 itself responds to stress as exposure of cells to H2O2-induced oxidative stress reduces FOXC1 levels and activity. Conditions that decrease FOXC1 function, such as exposure of cells to oxidative stress and FOXC1 ARS mutations, compromise the ability of TM cells to effectively respond to environmental stresses. Dysfunction of FOXC1 contributes to the death of TM cells, an important step in the development of glaucoma.
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