{Reference Type}: Journal Article
{Title}: Renal antiporter ClC-5 regulates collagen I/IV through the β-catenin pathway and lysosomal degradation.
{Author}: Durán M;Ariceta G;Semidey ME;Castells-Esteve C;Casal-Pardo A;Lu B;Meseguer A;Cantero-Recasens G;
{Journal}: Life Sci Alliance
{Volume}: 7
{Issue}: 7
{Year}: 2024 Jul
{Factor}: 5.781
{DOI}: 10.26508/lsa.202302444
{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 Clcn5 -/- ) present higher renal collagen deposition and fibrosis than WT mice. Altogether, we describe a new regulatory mechanism for collagens' production and release by ClC-5, which is altered in DD1 and provides a better understanding of disease progression to renal fibrosis.