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

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, accel...

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Main Authors: Jeong A. Han, Jong-Il Kim
Format: Article
Language:English
Published: BioMed Central 2017-06-01
Series:Genomics & Informatics
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Online Access:http://genominfo.org/upload/pdf/gni-15-56.pdf
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author Jeong A. Han
Jong-Il Kim
author_facet Jeong A. Han
Jong-Il Kim
author_sort Jeong A. Han
collection DOAJ
description 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.
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spelling doaj-art-34a5feb31e7e4fba8d1b92c04fb4f3d12025-02-02T06:17:17ZengBioMed CentralGenomics & Informatics1598-866X2234-07422017-06-01152566410.5808/GI.2017.15.2.56210Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX InhibitorsJeong A. Han0Jong-Il Kim1Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.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.http://genominfo.org/upload/pdf/gni-15-56.pdfcyclooxygenase 2fibroblastgene set enrichment analysisinhibitorsenescence
spellingShingle Jeong A. Han
Jong-Il Kim
Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
Genomics & Informatics
cyclooxygenase 2
fibroblast
gene set enrichment analysis
inhibitor
senescence
title Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
title_full Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
title_fullStr Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
title_full_unstemmed Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
title_short Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors
title_sort analysis of gene expression in human dermal fibroblasts treated with senescence modulating cox inhibitors
topic cyclooxygenase 2
fibroblast
gene set enrichment analysis
inhibitor
senescence
url http://genominfo.org/upload/pdf/gni-15-56.pdf
work_keys_str_mv AT jeongahan analysisofgeneexpressioninhumandermalfibroblaststreatedwithsenescencemodulatingcoxinhibitors
AT jongilkim analysisofgeneexpressioninhumandermalfibroblaststreatedwithsenescencemodulatingcoxinhibitors