Interactions between the circadian clock and TGF-β signaling pathway in zebrafish.

Autor: Sloin HE; School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Ruggiero G; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein, Germany., Rubinstein A; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel., Smadja Storz S; School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Foulkes NS; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein, Germany., Gothilf Y; School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Jun 25; Vol. 13 (6), pp. e0199777. Date of Electronic Publication: 2018 Jun 25 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0199777
Abstrakt: Background: TGF-β signaling is a cellular pathway that functions in most cells and has been shown to play a role in multiple processes, such as the immune response, cell differentiation and proliferation. Recent evidence suggests a possible interaction between TGF-β signaling and the molecular circadian oscillator. The current study aims to characterize this interaction in the zebrafish at the molecular and behavioral levels, taking advantage of the early development of a functional circadian clock and the availability of light-entrainable clock-containing cell lines.
Results: Smad3a, a TGF-β signaling-related gene, exhibited a circadian expression pattern throughout the brain of zebrafish larvae. Both pharmacological inhibition and indirect activation of TGF-β signaling in zebrafish Pac-2 cells caused a concentration dependent disruption of rhythmic promoter activity of the core clock gene Per1b. Inhibition of TGF-β signaling in intact zebrafish larvae caused a phase delay in the rhythmic expression of Per1b mRNA. TGF-β inhibition also reversibly disrupted, phase delayed and increased the period of circadian rhythms of locomotor activity in zebrafish larvae.
Conclusions: The current research provides evidence for an interaction between the TGF-β signaling pathway and the circadian clock system at the molecular and behavioral levels, and points to the importance of TGF-β signaling for normal circadian clock function. Future examination of this interaction should contribute to a better understanding of its underlying mechanisms and its influence on a variety of cellular processes including the cell cycle, with possible implications for cancer development and progression.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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