First look at the effect of overexpression of TIGR/MYOC on the transcriptome of the human trabecular meshwork.
Wild-type TIGR/MYOC is a secreted protein implicated in the development of steroid glaucoma. Mutations in TIGR/MYOC have been linked to some patients who develop elevated intraocular pressure (IOP) and glaucoma. Because there is evidence of some other factors contributing to the TIGR/MYOC causative role in glaucoma, and because substantial increased levels of a particular cellular mRNA and protein might alter expression of other host genes, we began to investigate the effect of TIGR/MYOC overexpression on the transcriptome of human trabecular meshwork cells. We used a recombinant adenovirus carrying wild-type TIGR/MYOC cDNA, primary HTM cells, 300 viral particles per cell and U133 Affymetrix GeneChips. Our results indicate that 2361 out of the 22,284 genes (10.6%) were altered more than two-fold (p<or=0.005) by the overexpression of TIGR/MYOC. A higher proportion of the altered genes were downregulated (1412 vs. 949). Potentially relevant upregulated genes include angiopoietin 2, matrix metalloproteinase 1 (MMP1) and thrombomodulin; among those downregulated we observed growth arrest specific 1, proteins involved in the ubiquitination pathway and vascular cell adhesion molecule 1. In addition, collagen type 1, one of the MMP1 substrates, was also downregulated. Genes affected by wild-type TIGR/MYOC might prove to be candidate mediators for future studies of the mechanisms of glaucoma.
Borrás
Teresa
T
Department of Ophthalmology, School of Medicine, University of North Carolina, at Chapel Hill, 6109 Neuroscience Research Building CB 7041, 103 Mason Farm Road, Chapel Hill, NC 27599-7041, USA. tborras@med.unc.edu
Bryant
Paul A
PA
Chisolm
Sarah S
SS
D042702:Angiopoietin-2 / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000032:analysis*; D015536:Down-Regulation / Q000235:genetics; D005136:Eye Proteins / Q000032:analysis* / Q000235:genetics; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000235:genetics*; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D018180:Thrombomodulin / Q000235:genetics; D014129:Trabecular Meshwork / Q000737:chemistry*; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000099179:Myocilin
D042702:Angiopoietin-2; D018797:Cell Cycle Proteins; D024042:Collagen Type I; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D020781:Matrix Metalloproteinase 1; D008565:Membrane Proteins; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D000099179:Myocilin; C096192:GAS1 protein, human