Parathyroid tissue transcriptome of control, untreated uremic and Cinacalcet-treated uremic rats at two timepoints
We investigate whether Cinacalcet treatment timed to the expression of its drug target; the Calcium-Sensing Receptor, could improve efficacy of treatment in secondary hyperparathyroidism. We found that proliferation rate of parathyroid glands of uremic rats was markedly reduced when Cinacalcet was administered in the early inactive phase compared to conventional timing early in the active phase. We use RNAseq of parathyroid tissue to investigate the possible mechanism behind this enhanced anti-proliferative effect. Overall design: CKD was induced by one-step 5/6 nephrectomy in 40 rats. After four weeks of uremia, 20 CKD rats were assigned to two treatment groups: Cina1 and Cina2 receiving Cinacalcet either morning (ZT2, N=10) or evening (ZT14, N=10), respectively. The remaining 20 untreated CKD rats were assigned to morning (PNX1, N=10) or evening (PNX2, N=10) investigation. Likewise, the 20 normal control rats were assigned to morning (ctrl1, N=10) or evening (ctrl2, N=10) investigation. After three weeks of treatment, parathyroid glands were investigated using Ki-67 immunostaining and RNAseq at the assigned time point, that is, morning (ZT2) for groups: Cina1, PNX1, and ctrl1, and evening (ZT14) for groups: Cina2, PNX2, and ctrl2.