| Autor: |
Wouter H. vanMegen, Teun J. vanHoutert, Caro Bos, Dorien J. M. Peters, Jeroen H. F. deBaaij, Joost G. J. Hoenderop |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Physiological Reports, Vol 12, Iss 7, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2051-817X |
| DOI: |
10.14814/phy2.15956 |
| Popis: |
Abstract Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid‐filled cysts in the kidney. In a subset of ADPKD patients, reduced blood calcium (Ca2+) and magnesium (Mg2+) concentrations are observed. As cystic fluid contains increased ATP concentrations and purinergic signaling reduces electrolyte reabsorption, we hypothesized that inhibiting ATP release could normalize blood Ca2+ and Mg2+ levels in ADPKD. Inducible kidney‐specific Pkd1 knockout mice (iKsp‐Pkd1−/−) exhibit hypocalcemia and hypomagnesemia in a precystic stage and show increased expression of the ATP‐release channel pannexin‐1. Therefore, we administered the pannexin‐1 inhibitor brilliant blue‐FCF (BB‐FCF) every other day from Day 3 to 28 post‐induction of Pkd1 gene inactivation. On Day 29, both serum Ca2+ and Mg2+ concentrations were reduced in iKsp‐Pkd1−/− mice, while urinary Ca2+ and Mg2+ excretion was similar between the genotypes. However, serum and urinary levels of Ca2+ and Mg2+ were unaltered by BB‐FCF treatment, regardless of genotype. BB‐FCF did significantly decrease gene expression of the ion channels Trpm6 and Trpv5 in both control and iKsp‐Pkd1−/− mice. Finally, no renoprotective effects of BB‐FCF treatment were observed in iKsp‐Pkd1−/− mice. Thus, administration of BB‐FCF failed to normalize serum Ca2+ and Mg2+ levels. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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