ArticleInvestigative ophthalmology & visual science2011
PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 33 citations in OpenAlex.
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- Ocular genetics in the genomics age.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Review
- Genetic association and differential expression of PITX2 with acute appendicitis.Human genetics · 2019Article
- Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye.PloS one · 2017Article
- Strain-Dependent Anterior Segment Dysgenesis and Progression to Glaucoma in Col4a1 Mutant Mice.Investigative ophthalmology & visual science · 2015Article
- PITX2C loss-of-function mutations responsible for idiopathic atrial fibrillation.Clinics (Sao Paulo, Brazil) · 2014Article
- Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family.Pflugers Archiv : European journal of physiology · 2014Review
- Prevalence and spectrum of PITX2c mutations associated with congenital heart disease.DNA and cell biology · 2013Article
- GPR158, an orphan member of G protein-coupled receptor Family C: glucocorticoid-stimulated expression and novel nuclear role.PloS one · 2013Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeMutations of the PITX2 gene cause Axenfeld-Rieger syndrome (ARS) and glaucoma. In this study, the authors investigated genes directly regulated by the PITX2 transcription factor to gain insight into the mechanisms underlying these disorders.
methodsRNA from nonpigmented ciliary epithelium cells transfected with hormone-inducible PITX2 and activated by mifepristone was subjected to microarray analyses. Data were analyzed using dCHIP algorithms to detect significant differences in expression. Genes with significantly altered expression in multiple microarray experiments in the presence of activated PITX2 were subjected to in silico and biochemical analyses to validate them as direct regulatory targets. One target gene was further characterized by studying the effect of its knockdown in a cell model of oxidative stress, and its expression in zebrafish embryos was analyzed by in situ hybridization.
resultsSolute carrier family 13 sodium-dependent dicarboxylate transporter member 3 (SLC13A3) was identified as 1 of 47 potential PITX2 target genes in ocular cells. PITX2 directly regulates SLC13A3 expression, as demonstrated by luciferase reporter and chromatin immunoprecipitation assays. Reduction of PITX2 or SLC13A3 levels by small interfering RNA (siRNA)-mediated knockdown augmented the death of transformed human trabecular meshwork cells exposed to hydrogen peroxide. Zebrafish slc13a3 is expressed in anterior ocular regions in a pattern similar to that of pitx2.
conclusionsThe results indicate that SLC13A3 is a direct downstream target of PITX2 transcriptional regulation and that levels of PITX2 and SLC13A3 modulate responses to oxidative stress in ocular cells.
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