Renal Ca2+ and Water Handling in Response to Calcium Sensing Receptor Signaling: Physiopathological Aspects and Role of CaSR-Regulated microRNAs

摘要

Calcium (Ca ) is a universal and vital intracellular messenger involved in a diverse range of cellular and biological processes. Changes in the concentration of extracellular Ca can disrupt the normal cellular activities and the physiological function of these systems. The calcium sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca and by other physiological cations, aminoacids, and polyamines. CaSR is the main controller of the extracellular Ca homeostatic system by regulating parathyroid hormone (PTH) secretion and, in turn, Ca absorption and resorption. Recent advances highlight novel signaling pathways activated by CaSR signaling involving the regulation of microRNAs (miRNAs). miRNAs are naturally-occurring small non-coding RNAs that regulate post-transcriptional gene expression and are involved in several diseases. We previously described that high luminal Ca in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through CaSR activation. Moreover, we demonstrated that CaSR signaling reduces AQP2 abundance via AQP2-targeting miRNA-137. This review summarizes the recent data related to CaSR-regulated miRNAs signaling pathways in the kidney.