Circadian gene expression in mouse renal proximal tubule

Abstract

Circadian variability in kidney function is well recognized but is often ignored as a potential confounding variable in physiological experiments. Here, we have created a data resource consisting of expression levels for mRNA transcripts in microdissected proximal tubule segments from mice as a function of the time of day. Small-sample RNA-sequencing (RNA-seq) was applied to microdissected S1 proximal convoluted tubules (PCTs) and S2 proximal straight tubules (PSTs). After stringent filtering, the data were analyzed using JTK-Cycle to detect periodicity. The dataset is provided as a user-friendly webpage at https://esbl.nhlbi.nih.gov/Databases/Circadian-Prox2/. In PCTs, 234 transcripts varied in a circadian manner (4.0 % of total). In PSTs, 334 transcripts varied in a circadian manner (5.3 %). Transcripts previously known to be associated with corticosteroid action and with increased flow were found to be overrepresented among circadian transcripts peaking during the "dark" portion of the day (Zeitgeber Time [ZT] 14-22), corresponding to the peak levels of corticosterone and glomerular filtration rate in mice. To ask whether there is time-of-day dependence of protein abundances in the kidney, we carried out LC-MS/MS-based proteomics in whole mouse kidneys at ZT12 and ZT0. The full data set (n=6546 proteins) is available at https://esbl.nhlbi.nih.gov/Databases/Circadian-Proteome/. Overall, 293 proteins were differentially expressed between ZT12 and ZT0 (197 greater at ZT12; 96 greater at ZT0). Among the regulated proteins, only 9 had been found to be periodic in the RNA-seq analysis, suggesting a high level of post-transcriptional regulation of protein abundances.