The role of lnc-TMPRSS15 when human lens epithelial cells exposed to dexamethosone
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193629 | GEO | 2022/01/16
REPOSITORIES: GEO
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Project description:Prolonged use of glucocorticoids can lead to the formation of a cataract, however the mechanism is not known. We recently reported the presence of the functional glucocorticoid receptor in immortalized cultured mammalian lens epithelial cells (Gupta & Wagner, Invest Ophthalmol Vis Sci 2003), but the short term biological effect of glucocorticoid action in lens epithelial cells is not known. This study seeks to examine glucocorticoid induced changes in global gene expression in LECs. RNA isolated from HLE B-3 cells, treated with Dex or Veh for 4 or 16 hours, was used to analyze global changes in gene expression by microarray hybridization. Microarray studies at 2 time periods demonstrate that glucocorticoids modulate gene expression in immortalized human LECs, reveal novel changes in gene expression, and confirms an endogenous genomic lens glucocorticoid response. Experiment Overall Design: HLE B-3 cells were treated with 1uM dexamethasone or vehicle for 4 or 16 hours in triplicate. Total RNA was converted to cRNA and hybridized to Affymetrix HUM_133A genechips. Images were acquired using the Affymetrix GeneArray scanner. Data was extracted using Affymetrix Microarray Suite 5.0.
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Project description:Differential expression of HSF4 in null newborn mouse and wildtype lenses was examined to identify putative downstream targets of HSF4. To examine roles of Brg1 in mouse lens development, a dnBrg1 transgenic construct was expressed using the lens-specific aA-crystallin promoter in postmitotic lens fiber cells. Morphological studies revealed abnormal lens fiber cell differentiation in transgenic lenses resulting in cataract. Electron microscopic studies showed abnormal lens suture formation and incomplete karyolysis (denucleation) of lens fiber cells. To identify genes regulated by Brg1, RNA expression profiling was performed in E15.5 embryonic wild type and dnBrg1 transgenic lenses. In addition, comparisons between differentially expressed genes in dnBrg1 transgenic, Pax6 heterozygous, and Hsf4 homozygous lenses identified multiple genes co-regulated by Brg1, Hsf4 and Pax6. Among them DNase IIb, a key enzyme required for lens fiber cell denucleation, was found downregulated in each of the Pax6, Brg1 and Hsf4 model systems. Lens-specific deletion of Brg1 using conditional gene targeting demonstrated that Brg1 was required for lens fiber cell differentiation and indirectly for retinal development but was not essential for lens lineage formation. Keywords: Differential mRNA Expression
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