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Permanent link (DOI): https://doi.org/10.7939/R32K9R
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Deciphering the Claudins that Mediate Renal Calcium Reabsorption Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
Desai, Prajakta V
- Supervisor and department
Alexander, Todd (Paediatrics)
- Examining committee member and department
Cheung, Po-Yin (Paediatrics)
Braam, Branko (Physiology)
- Date accepted
- Graduation date
Master of Science
- Degree level
Kidney stones and osteoporosis are prevalent clinical conditions posing a large
economic burden to the healthcare system. A common risk factor for both these
diseases is hypercalciuria, which is the inappropriate excretion of calcium in urine.
Changes in serum calcium levels are detected by the calcium sensing receptor (CaSR).
In the kidney, the CaSR is localized in tubular segments where calcium (Ca2+) flux
occurs via the paracellular pathway, specifically the proximal tubule and the thick
ascending limb of Henle’s loop (TAL). Claudins are proteins localized in the tight
junction of epithelia that control paracellular ion flux. Recently, claudin-14 (Cldn14)
expression was observed in the TAL. We found that Cldn14 is regulated by dietary
Ca2+ intake and by elevated serum Ca2+ levels after prolonged 1,25-dihydroxyvitamin
D3 administration in mice. Consistent with this, in vivo activation of the CaSR by
administration of the calcimimetic Cinacalcet, lead to a 40-fold increase in Cldn14
mRNA abundance. Overexpression of Cldn14 in a renal tubular cell culture model
inhibited paracellular Ca2+ flux. Together the data suggests that when serum Ca2+ level
increases it activates the CaSR leading to increased Cldn14 expression in the TAL.
This in turn blocks Ca2+ reabsorption and induces calciuria. Dysregulation of this
newly described CaSR-Cldn14 axis likely contributes to the development of
hypercalciuria and kidney stones.
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