title: Microgravity influences circadian clock oscillation in human keratinocytes.
abstract: 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 of Bmal1 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 of Rev-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.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Ranieri
authors.affiliation: Dipartimento di Chirurgia "P. Valdoni", Sapienza Università di Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
authors.affiliation: Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Alimandi
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy ; Azienda Ospedaliera S. Andrea, Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
keywords: Bmal1; Circadian clock; FAK, focal adhesion kinases; GPCR, G-protein-coupled receptors; Keratinocytes; Mechanotransduction; Microgravity; RPM, Random Positioning Machine; Rev-erbα; hg, hypergravity; mAbs, monoclonal antibodies