Microgravity influences circadian clock oscillation in human keratinocytes

Area of Science:

• Cell Biology
• Chronobiology
• Biophysics

Background:

• Gravitational forces significantly impact cellular functions and gene transcription via mechanotransduction pathways.
• Circadian clocks regulate numerous cellular and metabolic processes through molecular oscillations.

Purpose of the Study:

• To investigate the hypothesis that gravitational force changes influence epidermal cell physiology in sync with molecular clock oscillations.
• To explore the interplay between mechanosensitive pathways and circadian gene regulation in human keratinocytes.

Main Methods:

• Exposure of human keratinocytes to short simulated microgravity.
• Analysis of Bmal1 and Rev-erbα gene expression oscillations under varying gravitational conditions.
• Assessment of circadian clock gene feedback loop dynamics.

Main Results:

• Simulated microgravity exposure amplified Bmal1 circadian clock gene oscillations in human keratinocytes.
• Microgravity enhanced the amplitude of the Bmal1 feedback loop with reduced Rev-erbα transcriptional variability.
• Recovery from microgravity showed increased Bmal1 expression amplitude and prolonged Bmal1/Rev-erbα oscillatory periods.

Conclusions:

• Epidermal cells exhibit amplified circadian clock gene oscillations in response to simulated microgravity.
• Mechanotransduction pathways are integrated with circadian gene regulation, influencing cellular physiology.
• These findings suggest a novel network connecting mechanical forces to the molecular clock in skin cells.