ArticleThe Journal of clinical investigation2020
AGER1 downregulation associates with fibrosis in nonalcoholic steatohepatitis and type 2 diabetes.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Blocking AGEs reduces airway epithelial viral susceptibility in diabetes-exacerbated COPD.EMBO molecular medicine · 2026Article
- Article
- Role of neddylation in diabetes metabolism: potential therapeutic target.Journal of diabetes and metabolic disorders · 2026Review
- Hyperglycemia in Diabetes Drives Hepatic Fibrosis Through the Non-Enzymatic Function of HK2 and AGEs-mediated Matrix Stiffening.International journal of biological sciences · 2026Article
- DDOST mediates cervical cancer cell malignant progression by interacting with SMARCA4.American journal of cancer research · 2026Article
- Ferroptosis in liver fibrosis and its potential intervention strategy.Cell biology and toxicology · 2025Review
- Higher plasma dicarbonyl levels are associated with liver fibrosis in obese individuals.Diabetes, obesity & metabolism · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies.International journal of molecular sciences · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE/RAGE glycosylation.Frontiers in pharmacology · 2025Article
- The Emerging Role of Anti-Hyperglycemic Agents for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The Anti-AGEing and RAGEing Potential of Isothiocyanates.Molecules (Basel, Switzerland) · 2024Review
- Advanced glycation end products and reactive oxygen species: uncovering the potential role of ferroptosis in diabetic complications.Molecular medicine (Cambridge, Mass.) · 2024Review
- Article
- Macrophage RAGE activation is proinflammatory in NASH.JCI insight · 2024Article
- Article
- Liver directed adeno-associated viral vectors to treat metabolic disease.Journal of inherited metabolic disease · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. These findings were associated with necroinflammatory, fibrogenic, and pro-oxidant activity via the NADPH oxidase 4. Inhibition of AGEs or RAGE deletion in hepatocytes in vivo reversed these effects. We demonstrate that dysregulation of NRF2 by neddylation of cullin 3 was linked to AGER1 downregulation and that induction of NRF2 using an adeno-associated virus-mediated approach in hepatocytes in vivo reversed AGER1 downregulation, lowered the level of AGEs, and improved proinflammatory and fibrogenic responses in mice on a high AGEs diet. In patients with NASH and diabetes or insulin resistance, low AGER1 levels were associated with hepatocyte ballooning degeneration and ductular reaction. Collectively, prolonged exposure to AGEs in the liver promotes an AGER1/RAGE imbalance and consequent redox, inflammatory, and fibrogenic activity in NASH.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.