Identification of genes and transcription factors associated with glucocorticoid response in lens epithelial cells

Abstract

Prolonged glucocorticoids (GCs) treatment may lead to the formation of posterior subcapsular cataracts. The present study aimed to investigate differential gene expression in lens epithelial cells (LECs) in response to GCs using DNA microarray profiling. The gene expression profile of GSE13040 was downloaded from the Gene Expression Omnibus database, which includes 12 human LECs treated with vehicle or dexamethasone (Dex) for 4 or 16 h with six samples at each time period, of which three samples were treated with vehicle (control group) and three samples were treated with Dex (Dex group) at each time point. The differentially expressed genes (DEGs) were identified between the control group and the Dex group at each time period with the thresholds of P<0.05 and |logFC|>1. The DEGs were further analyzed using bioinformatics methods. Firstly, DEGs were subject to a hierarchical cluster analysis. Subsequently, the functional enrichment analysis was performed for the common DEGs between the two time periods. Finally, the transcription factors and binding sites of DEGs associated with response to GC stimulus were analyzed. A total of 696 and 949 DEGs were identified at 4 h and 16 h, respectively. Hierarchical cluster analysis revealed that DEG expression was higher in the Dex group than in the control group (P<0.05). A total of 13 significant functions were enriched for the 72 common DEGs at the two time periods. Chemokine (C-C motif) ligand 2 (CCL2), dual-specificity phosphatase-1 (DUSP1) and FAS were associated with the response to GC stimulus and the transcription factor c-Jun bound to promoter regulation regions of CCL2, DUSP1 and FAS. In conclusion, the transcription factors and binding sites of DEGs associated with the response of LECs to GCs may provide potential gene targets for designing and developing drugs to protect against GC-induced cataract formation.

Identification of Gene Changes Induced by Dexamethasone in the Anterior Segment of the Human Eye Using Bioinformatics Analysis

“…In another study, investigators posited that GCs downregulated expression of CCL2 in lens epithelial cells, suggesting a potential role for CCL2 in GC-induced cataracts [37]. Furthermore, this study also showed that the transcription factor c-Jun binds to the promoter regions of CCL2 to mediate its expression in the pathogenesis of GC-induced cataracts [37]. Hence, we conclude that CCL2 may participate in a variety of biological processes.…”

“…One study indicated that exogenous GILZ inhibits lipopolysaccharide-induced MCP-1 expression in rat retinal vascular endothelial cells through enhancing p65 dephosphorylation [36]. In another study, investigators posited that GCs downregulated expression of CCL2 in lens epithelial cells, suggesting a potential role for CCL2 in GC-induced cataracts [37]. Furthermore, this study also showed that the transcription factor c-Jun binds to the promoter regions of CCL2 to mediate its expression in the pathogenesis of GC-induced cataracts [37].…”

A quantitative transcriptomic analysis of the physiological significance of mTOR signaling in goat fetal fibroblasts

“…In the past several years, many studies have claimed that mTOR inhibition affects transcription by regulating the activation of specific transcription factors [27, 44]. Our transcriptomic analysis revealed 3 differentially expressed transcription factors—TCF20, NRL, and NFYB—the expression of which was related to mTORC1.…”

Glucocorticoid receptor signaling in the eye

“…In vitro studies using human lens epithelial cells (LEC) suggested that GCs affect cell proliferation, differentiation, apoptosis, survival, and migration, through non-genomic modulation of ERK/MAPK pathway [41]. Microarray analysis of LECs revealed multiple genes that were differentially regulated following DEX treatment compared to the control groups including upregulation in monocyte chemotactic protein-1 gene; CCL2 and downregulation of FAS receptor levels, an important cell surface receptor of the tumor necrosis factor receptor family, suggesting a potential role of inflammation in GC-induced cataract [42]. This finding was further supported by another study documenting that CCL2 was detected in patients’ samples following cataract surgery [43].…”