MicroRNAs modulate core-clock gene expression in pancreatic islets during early postnatal life in rats.

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State: Serval
Version: Author's accepted manuscript
Serval ID
serval:BIB_2B9A070B69A2
Type
Article: article from journal or magazin.
Collection
Publications
Title
MicroRNAs modulate core-clock gene expression in pancreatic islets during early postnatal life in rats.
Journal
Diabetologia
Author(s)
Jacovetti C., Rodriguez-Trejo A., Guay C., Sobel J., Gattesco S., Petrenko V., Saini C., Dibner C., Regazzi R.
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Publication state
Published
Issued date
10/2017
Peer-reviewed
Oui
Volume
60
Number
10
Pages
2011-2020
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Evidence continues to emerge detailing a fine-tuning of the regulation of metabolic processes and energy homeostasis by cell-autonomous circadian clocks. Pancreatic beta cell functional maturation occurs after birth and implies transcriptional changes triggered by a shift in the nutritional supply that occurs at weaning, enabling the adaptation of insulin secretion. So far, the developmental timing and exact mechanisms involved in the initiation of the circadian clock in the growing pancreatic islets have never been addressed.
Circadian gene expression was measured by quantitative RT-PCR in islets of rats at different postnatal ages up to 3 months, and by in vitro bioluminescence recording in newborn (10-day-old) and adult (3-month-old) islets. The effect of the microRNAs miR-17-5p and miR-29b-3p on the expression of target circadian genes was assessed in newborn rat islets transfected with microRNA antisense or mimic oligonucleotides, and luciferase reporter assays were performed on the rat insulin-secreting cell line INS832/13 to determine a direct effect. The global regulatory network between microRNAs and circadian genes was computationally predicted.
We found up to a sixfold-change in the 24 h transcriptional oscillations and overall expression of Clock, Npas2, Bmal1, Bmal2, Rev-erbα, Per1, Per2, Per3 and Cry2 between newborn and adult rat islets. Synchronisation of the clock machinery in cultured islet cells revealed a delayed cell-autonomous rhythmicity of about 1.5 h in newborn compared with adult rats. Computational predictions unveiled the existence of a complex regulatory network linking over 40 microRNAs displaying modifications in their expression profiles during postnatal beta cell maturation and key core-clock genes. In agreement with these computational predictions, we demonstrated that miR-17-5p and miR-29b-3p directly regulated circadian gene expression in the maturing islet cells of 10-day-old rats.
These data show that the circadian clock is not fully operational in newborn islets and that microRNAs potently contribute to its regulation during postnatal beta cell maturation. Defects in this process may have long-term consequences on circadian physiology and pancreatic islet function, favouring the manifestation of metabolic diseases such as diabetes.
Keywords
Animals, Animals, Newborn, Circadian Clocks/genetics, Circadian Rhythm Signaling Peptides and Proteins/genetics, Circadian Rhythm Signaling Peptides and Proteins/metabolism, Female, Gene Expression Regulation/physiology, Islets of Langerhans/metabolism, Male, MicroRNAs/genetics, MicroRNAs/metabolism, Rats, Rats, Sprague-Dawley, Circadian clock, MicroRNAs, Pancreatic islets, Postnatal maturation
Pubmed
Web of science
Open Access
Yes
Create date
27/07/2017 13:33
Last modification date
08/05/2019 16:21
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