Glucocorticoid-induced changes in the global gene expression of lens epithelial cells.
OBJECTIVE
Clinically, steroid use is accompanied by a risk for posterior subcapsular cataracts (PSCs). PSC possibly involves perturbation of lens epithelial cell proliferation and differentiation; however, the underlying mechanism is unknown. In this study, we aimed to characterize changes in gene expression in human lens epithelial cells exposed to glucocorticoid using DNA microarray hybridization.


METHODS
Human lens epithelial cells (HLE B-3) were treated with dexamethasone (1 microM) for 24 or 48 hours or with vehicle (0.01% dimethylsulfoxide) and the derived cRNA was hybridized to U133A microarrays. Data were processed using the Affymetrix program Micro Array Suite, and ontological analyses were performed using the software dChip, filtering to exclude transcripts up- or down-regulated by less than 2-fold.


RESULTS
At 24 hours, 57 transcripts were upregulated relative to controls by greater than 2- fold and 50 were downregulated by greater than 2-fold. At 48 hours, 92 transcripts were upregulated and 42 were downregulated. Twenty-two upregulated and 2 downregulated transcripts were shared between the 24-hour and 48-hour data sets. The predominant ontological groupings were: signal transduction, transcription factor activity, cytoskeleton/ECM/adhesion, transport, and cell cycle/development. Alternate ontological interpretations are possible.


CONCLUSIONS
The data indicate steroid treatment of lens epithelial cells is associated with significant changes in gene expression in several functional categories and these include transcripts related to cell proliferation.
James
Eric R
ER
Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, SC 29403, USA. jameser@musc.edu
Fresco
Victor M
VM
Robertson
Lorie L
LL
D002460:Cell Line; D016208:Databases, Factual; D003907:Dexamethasone / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D015854:Up-Regulation
D005938:Glucocorticoids; D003907:Dexamethasone; D004121:Dimethyl Sulfoxide