Microgravity influences circadian clock oscillation in human keratinocytes
Danilo Ranieri ; Alessandra Cucina ; Mariano Bizzarri ; et al.
Jan - 2015
DOI: 10.1016/j.fob.2015.08.012

journal : FEBS Open Bio

Volume : 5 ; Issue : 1
type: Article Journal

Microgravity and sudden changes of gravitational forces exert numerous effects on tissues, organs and apparatus. Responses to these forces variably applied to cells indicate the existence of mechanotransduction pathways able to modulate transcription. Oscillation of circadian clocks similarly influences many cellular and metabolic processes. Here we hypothesized that signals derived from changes of gravitational forces applied to epidermal cells might influence their physiology in harmony with the oscillation of the molecular clock. In this study, we describe amplified oscillations ofBmal1 circadian clock gene in human keratinocytes exposed to short simulated microgravity and to rapid variation of gravitational forces. We found that exposure to microgravity enhances the amplitude of the Bmal1 feedback loop sustained by an apparently lower variability ofRev-erbα transcription, while recovery from microgravity is characterized by increased amplitude of Bmal1 expression and elongation of the oscillatory periods of Bmal1 and Rev-erbα. These data highlight the existence of integrated signaling network connecting mechanosensitive pathways to circadian gene regulation.

keywords : FAK; focal adhesion kinases; GPCR;G-protein-coupled receptors; hg ; hypergravity; mAbs; monoclonal antibodies; RPM;Random Positioning Machine; Microgravity; Circadian clock; Mechanotransduction; Bmal1; Rev-erbα; Keratinocytes

Notes : AcknowledgmentsThis work was partially supported by Grants from ASI – Italian Space Agency (I/003/11/0 and 2014-010-R.0) [...]