| First Author | Verschuren EHJ | Year | 2018 |
| Journal | Am J Physiol Renal Physiol | Volume | 315 |
| Issue | 3 | Pages | F537-F546 |
| PubMed ID | 29767557 | Mgi Jnum | J:279824 |
| Mgi Id | MGI:6367939 | Doi | 10.1152/ajprenal.00622.2017 |
| Citation | Verschuren EHJ, et al. (2018) Polycystin-1 dysfunction impairs electrolyte and water handling in a renal precystic mouse model for ADPKD. Am J Physiol Renal Physiol 315(3):F537-F546 |
| abstractText | The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp- Pkd1(-/-)) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp- Pkd1(-/-) mice display reduced serum levels of magnesium (Mg(2+)), calcium (Ca(2+)), sodium (Na(+)), and phosphate (Pi) compared with control ( Pkd1(+/+)) mice and renal Mg(2+), Ca(2+), and Pi wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of iKsp- Pkd1(-/-) mice compared with controls. Similarly, decreased renal gene expression of markers for TAL ( Umod) and DCT ( Pvalb) was observed in iKsp- Pkd1(-/-) mice. Conversely, mRNA expression levels in kidney of genes encoding solute and water transporters in the proximal tubule ( Abcg2 and Slc34a1) and collecting duct ( Aqp2, Scnn1a, and Scnn1b) remained comparable between control and iKsp- Pkd1(-/-) mice, although a water reabsorption defect was observed in iKsp- Pkd1(-/-) mice. In conclusion, our data indicate that PC1 is involved in renal Mg(2+), Ca(2+), and water handling and its dysfunction, resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations. |
