Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors

  • Han, Jeong A. (Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine) ;
  • Kim, Jong-Il (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
  • Received : 2017.03.31
  • Accepted : 2017.05.04
  • Published : 2017.06.30
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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 ${\beta}$ 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.

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References

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