Chronic stress-driven glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic...

Area of Science:

• Molecular Biology
• Cell Biology
• Environmental Health

Background:

• Chronic environmental stress affects cellular and organismal function.
• Epigenetics is a key mediator linking environmental exposures to health outcomes.
• Glucocorticoid stress hormones, like cortisol, act via the glucocorticoid receptor (GR) to mediate genomic effects of stress.

Purpose of the Study:

• To investigate how chronic stress-driven GR activation influences epigenetic modifications and cell states.
• To dissect the molecular mechanisms by which cortisol affects fibroblast function.

Main Methods:

• Human fibroblasts were exposed to cortisol and/or a GR antagonist.
• Cell proliferation, migration, and morphology were assessed.
• Changes in DNA methylation and mRNA expression were analyzed genome-wide.

Main Results:

• Cortisol induced significant changes in cell proliferation, migration, and morphology.
• These cortisol-induced effects were blocked by concomitant GR antagonism.
• Widespread, context-dependent alterations in DNA methylation and mRNA expression were observed, affecting genes involved in cell motility and proliferation.

Conclusions:

• GR activation by cortisol drives specific cell phenotypes.
• These phenotypes are associated with broad epigenomic changes, including DNA methylation and gene expression.
• Findings illuminate how stress-induced epigenomic patterns shape cellular functions and contribute to health.