ArticleCell death & disease2020
Elevated intracellular copper contributes a unique role to kidney fibrosis by lysyl oxidase mediated matrix crosslinking.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 97 citations in OpenAlex.
- Copper Metabolism-Related Cell Death in Kidney Diseases: Molecular Mechanisms, Disease-Specific Evidence, and Translational Implications.International journal of molecular sciences · 2026Review
- An Investigation of Elevated Serum Copper Levels Following Bariatric Surgery.Obesity surgery · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Xuefu Zhuyu Decoction Reduces Excessive Collagen Deposition and Crosslinking in Myocardial Fibrosis via CTR1-Copper-LOX Axis.Chinese journal of integrative medicine · 2026Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- ATP7A-fibulin-4 complex delivers copper in the Golgi to activate LOX in renal fibrosis.JCI insight · 2026Article
- Trientine ameliorates bleomycin-induced pulmonary fibrosis in rats through copper chelation and modulation of the CTR1/LOX/COL pathway.Inflammopharmacology · 2026Article
- Unraveling the role of cuproptosis in pulmonary fibrosis pathogenesis and prognosis: an integrative single-cell transcriptomics and microarray analysis.Molecular and cellular biochemistry · 2026Article
- SLC31A1 exon 1 methylation reduces intracellular copper ion and promotes diabetic cardiac fibrosis.Cardiovascular diabetology · 2026Article
- Copper-Targeted Therapy in Experimental Endometriosis: Effects of Ammonium Tetrathiomolybdate on Markers of the Interconnected Processes of Inflammation, Innervation, and Fibrogenesis.International journal of molecular sciences · 2026Article
- Article
- Magnesium, Zinc and Copper in Lung Fibrosis: A Narrative Review.Medicina (Kaunas, Lithuania) · 2025Review
- Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases.Renal failure · 2025Review
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- Development and validation of multi-center serum creatinine-based models for noninvasive prediction of kidney fibrosis in chronic kidney disease.Renal failure · 2025Article
- Role and mechanisms of cuproptosis in the pathogenesis of Wilson's disease (Review).International journal of molecular medicine · 2025Review
- Tetrathiomolybdate alleviates bleomycin-induced pulmonary fibrosis by reducing copper concentration and suppressing EMT.European journal of medical research · 2025Article
- Single-cell RNA sequencing reveals SLC31A1-mediated M2 polarization of macrophages promotes malignant progression in triple-negative breast cancer.Journal of cancer research and clinical oncology · 2025Article
- Hepatic microtubule destabilization facilitates liver fibrosis in the mouse model of Wilson disease.Journal of molecular medicine (Berlin, Germany) · 2025Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 renal fibroblast cells using chromatin immunoprecipitation. Elevated CTR1 induced increase of copper intracellular influx. The elevated intracellular copper ions activated lysyl oxidase (LOX) to enhance the crosslinking of collagen and elastin, which then promoted kidney fibrosis. Reducing intracellular copper accumulation by knocking down CTR1 ameliorated kidney fibrosis in unilateral ureteral obstruction induced renal fibrosis model and renal fibroblast cells stimulated by TGF-β. Treatment with copper chelator tetrathiomolybdate (TM) also alleviated renal fibrosis in vivo and in vitro. In conclusion, intracellular copper accumulation plays a unique role to kidney fibrosis by activating LOX mediated collagen and elastin crosslinking. Inhibition of intracellular copper overload may be a potential portal to alleviate kidney fibrosis.
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