Parathyroid hormone (PTH) regulates serum calcium levels and bone strength. Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality. In experimental SHP, the increased PTH gene expression is due to increased PTH mRNA stability and is mediated by protein-PTH mRNA interactions. AUF1 (adenosine-uridine-rich binding factor 1) stabilizes and KSRP (K-homology splicing regulatory protein) destabilizes PTH mRNA. The 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. A further level of post-transcriptional regulation occurs through miRNA. Dicer mediates the final step of miRNA maturation. Parathyroid-specific Dicer knockout mice that lack miRNAs in the parathyroid develop normally. Surprisingly, these mice fail to increase serum PTH in response to both hypocalcemia and CKD, indicating that parathyroid Dicer and miRNAs are essential for stimulation of the parathyroid. 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. let-7 and miR-148 antagonism modifies PTH secretion in vivo and in vitro, suggesting roles for specific miRNAs in parathyroid function. This review summarizes 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.This article is protected by copyright. All rights reserved.
February 18, 2020
Physiotherapists’ experiences of managing persons with suspected cauda equina syndrome: Overcoming the challenges.
October 8, 2020
February 13, 2020
- ENDO: 2020ENDO 2020 Annual Conference has been canceled due to COVID-19. Here are highlights of emerging data that has still been released. Keep an eye out for ENDO Online 2020, which will take place from June 8 to 22.