ArticleInternational journal of biological sciences2025
Smad3 Mediates Renal Fibrosis via GPX4-Dependent Ferroptosis.
Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on transfusion and intravenous iron use in chronic kidney disease anemia: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- CYP1B1 is a potential target of kaempferol in renal fibrosis: a multi‑omics and single‑cell transcriptomics study.Bioresources and bioprocessing · 2026Article
- Animal models of anemia of inflammation: Methodological advances, limitations, and translational applications.Animal models and experimental medicine · 2026Review
- Quercetin Alleviates Ferroptosis-Induced Renal Fibrosis by Modulating the PRDM9/HMOX1/PTGS2 Axis.ACS omega · 2026Article
- Natural product therapy in diabetic kidney disease: emerging multiomics-mediated signalling pathway and molecular target.Chinese medicine · 2026Review
- The inflammatory-autophagy-NETs axis in renal fibrosis: mechanistic crosstalk and pathological feed-forward amplification loops.Molecular and cellular biochemistry · 2026Review
- Ablation of the renal tubular gluconeogenic enzyme PCK1 drives AKI-to-CKD transition by negatively regulating the TGF-β/Smad3 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Review
- Cellular senescence of renal tubular epithelial cells in diabetic kidney disease: emerging mechanisms and targeted interventions.Frontiers in cell and developmental biology · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
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Authors and funding
9 authors.
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Abstract
TGF-β/Smad3 signaling is a key pathway leading to the cell death and renal fibrosis. Here we report a new mechanism through which Smad3 mediates renal fibrosis by downregulating the glutathione peroxidase 4 (GPX4), a central inhibitor for ferroptosis. In patients with chronic kidney disease (CKD) and a mouse model of unilateral ureteral obstruction (UUO), progressive renal fibrosis was associated with the overactive Smad3 signaling and the development of ferroptosis identified by decreased GPX4 while increasing two ferroptosis biomarkers including the Transferrin receptor 1 (TFR1) and 4-Hydroxynonenal (4-HNE). Mechanistically, we uncovered that Smad3 could bind directly to GPX4 to repress its transcription while increasing TFR1 and 4-HNE expression, which was abolished when this binding site was mutated. This novel finding was functionally confirmed in the UUO mice and mouse embryonic fibroblasts (MEFs) in which deletion of Smad3 protected against UUO and transforming growth factor-β1 (TGF-β1)-induced loss of GPX4, upregulation of TFR1 and 4-HNE, and progressive renal fibrosis
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