PT  - JOURNAL ARTICLE
AU  - Durán, Mònica
AU  - Ariceta, Gema
AU  - Semidey, Maria E
AU  - Castells-Esteve, Carla
AU  - Casal-Pardo, Andrea
AU  - Lu, Baisong
AU  - Meseguer, Anna
AU  - Cantero-Recasens, Gerard
TI  - Renal antiporter ClC-5 regulates collagen I/IV through the β-catenin pathway and lysosomal degradation
AID  - 10.26508/lsa.202302444
DP  - 2024 Jul 01
TA  - Life Science Alliance
PG  - e202302444
VI  - 7
IP  - 7
4099  - https://www.life-science-alliance.org/content/7/7/e202302444.short
4100  - https://www.life-science-alliance.org/content/7/7/e202302444.full
SO  - Life Sci. Alliance2024 Jul 01; 7
AB  - 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.The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials. Correspondence and material requests should be addressed to G Cantero-Recasens (Gerard.cantero{at}vhir.org) or A Meseguer (ana.meseguer{at}vhir.org).