Elevated intracellular copper contributes a unique role to kidney fibrosis by lysyl oxidase mediated matrix crosslinking.

ABSTRACT: Copper ions play various roles in mammalian cells, presumably due to their involvement in different enzymatic reactions. Some studies indicated that serum copper correlates with fibrosis in organs, such as liver and lung. However, the mechanism is unknown. Here, we explored the role of copper in kidney fibrosis development and possible underlying mechanisms. We found that copper transporter 1 (CTR1) expression was increased in the kidney tissues in two fibrosis models and in patients with kidney fibrosis. Similar results were also found in renal tubular epithelial cells and fibroblast cells treated with transforming growth factor beta (TGF-β). Mechanistically, the upregulation of CTR1 required Smads-dependent TGF-β signaling pathway and Smad3 directly binded to the promoter of CTR1 in rena

SUBMITTER: Niu YY 

PROVIDER: S-EPMC7109154 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature