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Publication : Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa.

First Author  Ihara T Year  2017
Journal  PLoS One Volume  12
Issue  1 Pages  e0168234
PubMed ID  28060940 Mgi Jnum  J:246118
Mgi Id  MGI:5916806 Doi  10.1371/journal.pone.0168234
Citation  Ihara T, et al. (2017) Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa. PLoS One 12(1):e0168234
abstractText  OBJECTIVES: ClockDelta19/Delta19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockDelta19/Delta19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes. MATERIALS AND METHODS: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockDelta19/Delta19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used. Gene expression rhythms and transcriptional regulation mechanisms in clock genes, mechanosensor, Cx26 and VNUT were measured in the mouse bladder mucosa, collected every 4 hours from WT and ClockDelta19/Delta19 mice using quantitative RT-PCR, a Western blot analysis, and ChIP assays. RESULTS: WT mice showed circadian rhythms in clock genes as well as mechanosensor, Cx26 and VNUT. Their expression was low during the sleep phase. The results of ChIP assays showed Clock protein binding to the promotor regions and the transcriptional regulation of mechanosensor, Cx26 and VNUT. In contrast, all of these circadian expressions were disrupted in ClockDelta19/Delta19 mice. The gene expression of mechanosensor, Cx26 and VNUT was maintained at a higher level in spite of the sleep phase. CONCLUSIONS: Mechanosensor, Cx26 and VNUT expressed with circadian rhythm in the mouse bladder mucosa. The disruption of circadian rhythms in these genes, induced by the abnormalities in clock genes, may be factors contributing to NOC because of hypersensitivity to bladder wall extension.
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