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

Area of Science:

• Biochemistry
• Dermatology
• Molecular Biology

Background:

• Cyclooxygenase-2 (COX-2) selective inhibitors, NS-398 and celecoxib, and the non-selective inhibitor aspirin, exhibit differential effects on cellular senescence and skin aging.
• Previous studies indicated NS-398 inhibits senescence, while celecoxib and aspirin accelerate it.

Purpose of the Study:

• To elucidate the distinct molecular mechanisms underlying the senescence-modulating effects of different COX inhibitors.
• To identify specific gene sets regulated by NS-398, celecoxib, and aspirin in the context of cellular senescence.

Main Methods:

• Utilized cDNA microarray analysis to assess gene expression profiles following treatment with NS-398, celecoxib, and aspirin.
• Performed Gene Set Enrichment Analysis (GSEA) to identify regulated senescence-related gene sets.

Main Results:

• NS-398 treatment upregulated gene sets associated with the tumor necrosis factor β receptor pathway and fructose/mannose metabolism, while downregulating protein secretion pathways.
• Celecoxib upregulated gene sets involved in the G2M checkpoint and E2F targets.
• Aspirin upregulated protein secretion pathways and downregulated RNA transcription pathways.

Conclusions:

• COX inhibitors modulate cellular senescence through diverse molecular mechanisms.
• The findings provide valuable insights into the differential regulation of senescence by various COX inhibitors, contributing to a deeper understanding of aging processes.