ArticleScientific reports2017
D-serine, a novel uremic toxin, induces senescence in human renal tubular cells via GCN2 activation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Gut Microbiota and Their Metabolites in Acute Kidney Injury: Classification, Mechanisms, and Therapeutic Potential.Metabolites · 2026Review
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Understanding and targeting senescence in kidney disease.Clinical kidney journal · 2025Review
- Urinary metabolomics analysis of patients with renal tubular dysfunction after PCI surgery.International urology and nephrology · 2025Article
- Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage.International journal of molecular sciences · 2025Article
- Detection of Fast Decliner of Diabetic Kidney Disease Using Chiral Amino Acid Profiling: A Pilot Study.Chemistry & biodiversity · 2025Article
- L-serine metabolic regulation and host respiratory homeostasis.Frontiers in cellular and infection microbiology · 2025Review
- Chiral Amino Acids Mediate Mitochondria-Dependent Apoptosis of Human Proximal Tubular Epithelial Cells Under Oxidative Stress.International journal of molecular sciences · 2024Article
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- Predictive value of serum d-serine level for hearing impairment in uremic patients.Renal failure · 2023Article
- Exploratory metabolomic analysis based on UHPLC-Q-TOF-MS/MS to study hypoxia-reoxygenation energy metabolic alterations in HK-2 cells.Renal failure · 2023Article
- The AKI-to-CKD Transition: The Role of Uremic Toxins.International journal of molecular sciences · 2023Review
- Gut microbiota and neonatal acute kidney injury biomarkers.Pediatric nephrology (Berlin, Germany) · 2023Review
- D-Serine as a sensor and effector of the kidney.Clinical and experimental nephrology · 2023Review
- Correlation study of FGF23/D-serine in maintenance hemodialysis patients with combined hearing impairment.PloS one · 2023Article
- Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine?International journal of molecular sciences · 2022Article
- Cellular senescence: the good, the bad and the unknown.Nature reviews. Nephrology · 2022Review
- In vitro study on effect of bardoxolone methyl on cisplatin-induced cellular senescence in human proximal tubular cells.Molecular and cellular biochemistry · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevalence of chronic kidney disease (CKD), characterized by progressive renal dysfunction with tubulointerstitial fibrosis, is increasing because of societal aging. Uremic toxins, accumulated during renal dysfunction, cause kidney damage, leading to renal deterioration. A recent metabolomic analysis revealed that plasma D-serine accumulation is associated with faster progression of renal dysfunction in CKD patients. However, the causal relationship and the underlying mechanisms remain unclear. Herein, we demonstrated that D-serine markedly induced cellular senescence and apoptosis in a human proximal tubular cell line, HK-2, and primary culture of human renal tubular cells. The former was accompanied by G2/M cell cycle arrest and senescence-associated secretory phenotype, including pro-fibrotic and pro-inflammatory factors, contributing to tubulointerstitial fibrosis. Integrated stress response mediated by the general control nonderepressible 2 played an important role in D-serine-induced tubular cell toxicity and pro-fibrotic phenotypes, accelerating CKD progression and kidney aging. D-serine upregulated the L-serine synthesis pathway. Furthermore, D-serine-induced suppression of tubular cell proliferation was ameliorated by L-serine administration, indicating that D-serine exposure induced an L-serine-deprived state in tubular cells, compensated by L-serine synthesis. Thus, this study unveils molecular mechanisms underlying D-serine-induced tubular damage and pro-fibrotic phenotypes, suggesting that D-serine is a uremic toxin involved in CKD pathogenesis.
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