Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors.
- Author:
Jeong A HAN
1
;
Jong Il KIM
Author Information
- Publication Type:Original Article
- Keywords: cyclooxygenase 2; fibroblast; gene set enrichment analysis; inhibitor; senescence
- MeSH: Aging; Animals; Aspirin; Celecoxib; Cell Aging; Cyclooxygenase 2; Fibroblasts*; Fructose; Gene Expression*; Genes, vif; Humans*; Mannose; Metabolism; Mice; Mice, Hairless; Oligonucleotide Array Sequence Analysis; RNA; Skin Aging; Tumor Necrosis Factor-alpha
- From:Genomics & Informatics 2017;15(2):56-64
- CountryRepublic of Korea
- Language:English
- Abstract: We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)–selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2–selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor β receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.
