Genomics Inform.  2017 Jun;15(2):56-64. 10.5808/GI.2017.15.2.56.

Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors

• Han JA
• Kim JI

• KMID: 2384032
• DOI: http://doi.org/10.5808/GI.2017.15.2.56

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.

Keyword

cyclooxygenase 2; fibroblast; gene set enrichment analysis; inhibitor; senescence

MeSH Terms

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
Aspirin
Celecoxib
Cyclooxygenase 2
Fructose
Mannose
RNA
Tumor Necrosis Factor-alpha