A new article published in The FEBS Journal reported that secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality. In experimental SHP, the increased parathyroid hormone (PTH) gene expression is due to increased PTH mRNA stability and is mediated by protein-PTH mRNA interactions. While AUF1 (adenosine-uridine-rich binding factor 1) stabilizes, KSRP (K-homology splicing regulatory protein) destabilizes PTH mRNA.

On the other hand, peptidyl-prolyl cis/trans isomerase Pin1 acts on target proteins, including mRNA-binding proteins. Pin1 leads to KSRP dephosphorylation, but in SHP, parathyroid Pin1 activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, leading to increased PTH mRNA stability and levels.

Further post-transcriptional regulation occurs through miRNA. Dicer mediates the final step of miRNA maturation. Human and rodent parathyroids share similar miRNA profiles that are altered in hyperparathyroidism. The evolutionary conservation of abundant miRNAs and their regulation in hyperparathyroidism indicate their significance in parathyroid physiology and pathophysiology.

In addition, let-7 and miR-148 antagonism modifies PTH secretion in vivo and in vitro, suggesting roles for specific miRNAs in parathyroid function. Thus, this review summarized the current knowledge on the post-transcriptional mechanisms of PTH gene expression in SHP and the central contribution of miRNAs to the high serum PTH levels of both primary and SHP.

Source: The FEBS Journal. 2020 Mar 19. doi: 10.1111/febs.15300.