| First Author | Dimke H | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 6 | Pages | F761-9 |
| PubMed ID | 23283989 | Mgi Jnum | J:194355 |
| Mgi Id | MGI:5473471 | Doi | 10.1152/ajprenal.00263.2012 |
| Citation | Dimke H, et al. (2013) Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion. Am J Physiol Renal Physiol 304(6):F761-9 |
| abstractText | Kidney stones are a prevalent clinical condition imposing a large economic burden on the healthcare system. Hypercalciuria remains the major risk factor for development of a Ca(2+)-containing stone. The kidney's ability to alter Ca(2+) excretion in response to changes in serum Ca(2+) is in part mediated by the Ca(2+)-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca(2+) intake and by elevated serum Ca(2+) levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca(2+) flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca(2+). This molecular mechanism likely facilitates renal Ca(2+) losses in response to elevated serum Ca(2+). Moreover, dysregulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. |
