ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
GLP-1 Receptor Agonists Alleviate Diabetic Kidney Injury via β-Klotho-Mediated Ferroptosis Inhibition.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Gut‑liver‑kidney axis: A systems biology framework for understanding and treating chronic kidney disease (Review).International journal of molecular medicine · 2026Review
- Comparative effects of semaglutide tirzepatide and retatrutide on renal fibrosis in UUO and aged mice.iScience · 2026Article
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- Phytochemicals and Irisin as Multi-Target Regulators of Adipose Tissue Browning and Metabolic Reprogramming: Synergies with GLP-1 Pathways.Antioxidants (Basel, Switzerland) · 2026Review
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Amelioration of Cisplatin Nephrotoxicity by Fe-Pt Coordination Exchange-Triggered Ferroptosis Suppression.Advanced healthcare materials · 2026Article
- Dulaglutide vs insulin in adolescents with thalassaemia-induced diabetes: effect on metabolism and atherogenesis (DIADEMA).Diabetologia · 2026Article
- Review
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Mesenchymal Stem Cells Attenuate Diabetic Nephropathy by Suppressing the ERK-Ferroptosis-ROS Axis.International journal of molecular sciences · 2026Article
- Dual-targeted engineered mesenchymal stem cell-derived extracellular vesicles delivering Nedd4 attenuate renal fibrosis in diabetic kidney disease.Materials today. Bio · 2026Article
- Multimodal Magnetic Resonance Imaging in Diabetic Kidney Disease: From Pathophysiological Insights to Clinical Applications.Diagnostics (Basel, Switzerland) · 2026Review
- Semaglutide targets the Isg15-FUNDC1 axis: suppressing IFN-β overactivation and attenuating blood-brain barrier injury in diabetic intracerebral hemorrhage.Journal of neuroinflammation · 2026Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Metabolic pathways and cell death modalities in diabetic complications: unraveling pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.Cell death discovery · 2026Review
- GLP-1 Receptor Agonists in Chronic Inflammatory Skin Diseases: Immunometabolic Mechanisms and Translational Perspectives.Pharmaceutics · 2026Review
- Emerging Role of Ferroptosis in Diabetes and Associated Complications: When Metabolic Dysregulation Meets Cell Death.Cell proliferation · 2026Review
- Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Association of glucagon-like peptide-1 receptor agonist use with clinical outcomes in patients with rheumatoid arthritis and type 2 diabetes.Journal of diabetes investigation · 2026Article
- Glucagon-Like Peptide-1 Receptor Agonists in Chronic Kidney Disease: Mechanisms and Clinical Perspectives.Kidney medicine · 2026Review
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Authors and funding
12 authors.
Funding
Abstract
Semaglutide (Smg), a GLP-1 receptor agonist (GLP-1RA), shows renal protective effects in patients with diabetic kidney disease (DKD). However, the exact underlying mechanism remains elusive. This study employs transcriptome sequencing and identifies β-Klotho (KLB) as the critical target responsible for the role of Smg in kidney protection. Smg treatment alleviates diabetic kidney injury by inhibiting ferroptosis in patients, animal models, and HK-2 cells. Notably, Smg treatment significantly increases the mRNA expression of KLB through the activation of the cyclic adenosine monophosphate (cAMP) signaling pathway, specifically through the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Subsequently, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway is activated, reprograming the key metabolic processes of ferroptosis such as iron metabolism, fatty acid synthesis, and the antioxidant response against lipid peroxidation. Suppression of ferroptosis by Smg further attenuates renal inflammation and fibrosis. This work highlights the potential of GLP-1RAs and KLB targeting as promising therapeutic approaches for DKD management.
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