Renal antiporter ClC-5 regulates collagen I/IV through the β-catenin pathway and lysosomal degradation.

ABSTRACT: Mutations in Cl^-/H⁺ antiporter ClC-5 cause Dent's disease type 1 (DD1), a rare tubulopathy that progresses to renal fibrosis and kidney failure. Here, we have used DD1 human cellular models and renal tissue from DD1 mice to unravel the role of ClC-5 in renal fibrosis. Our results in cell systems have shown that ClC-5 deletion causes an increase in collagen I (Col I) and IV (Col IV) intracellular levels by promoting their transcription through the β-catenin pathway and impairing their lysosomal-mediated degradation. Increased production of Col I/IV in ClC-5-depleted cells ends up in higher release to the extracellular medium, which may lead to renal fibrosis. Furthermore, our data have revealed that 3-mo-old mice lacking ClC-5 (Clcn5 ^+/- and

SUBMITTER: Duran M 

PROVIDER: S-EPMC11053357 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature