ArticleInternational journal of molecular sciences2022
Dapagliflozin Prevents High-Glucose-Induced Cellular Senescence in Renal Tubular Epithelial Cells.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Inhibition of SGLT2 reduces blood pressure in the early phase of salt-sensitive hypertension in male Dahl-SS rats independently of changes in renal inflammation.Physiological reports · 2026Article
- Molecular mechanisms and therapeutic strategies of glomerular cell senescence in diabetic kidney disease: from heterogeneity to precision intervention.Cellular and molecular life sciences : CMLS · 2026Review
- Dual Modulation of Senescence and Immune Checkpoints by Metformin and Dapagliflozin Attenuates Liver Fibrosis in a Thioacetamide-Induced Rat Model.Advanced pharmaceutical bulletin · 2026Article
- γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate NADPH-Driven Oxidative Stress.Biomolecules & therapeutics · 2026Article
- Diabetes and its complications: molecular mechanisms, prevention and treatment.Signal transduction and targeted therapy · 2026Review
- From a Shared Stress to Cell-Type-Specific Responses: The Heterogeneous Mechanisms of High Glucose-Induced Cellular Senescence in Diabetic Kidney Disease.Journal of diabetes research · 2026Review
- Breaking barriers in pulmonary health of patients with metabolic diseases: senolytics and beyond.Frontiers in aging · 2026Review
- Enhanced Selenium Supplement Extends Lifespan and Delays Multi-Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adipose immune microenvironment: catalyst of age-related adipose tissue dysfunction.Immunity & ageing : I & A · 2025Review
- Biomarkers of Cellular Senescence in Type 2 Diabetes Mellitus.Aging cell · 2025Article
- Activation of NR2A-Wnt-TLR2 Signaling Axis in Satellite Glial Cells of the Dorsal Root Ganglion Contributes to Neuropathic Pain Induced by Nerve Injury in Diabetic Mice.Molecular neurobiology · 2025Article
- Dapagliflozin's Effects on Urinary Albumin and Non-Albumin Proteins in Diabetic and Non-Diabetic Kidney Transplant Recipients.Biomedicines · 2025Article
- SGLT2 inhibitors as a novel senotherapeutic approach.npj aging · 2025Review
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell.Frontiers in endocrinology · 2025Article
- Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.Journal of applied biomedicine · 2024Article
- The senescence-associated secretory phenotype and its physiological and pathological implications.Nature reviews. Molecular cell biology · 2024Review
- Bioinformatic analyses reveal lysosomal-associated protein transmembrane 5 as a potential therapeutic target in lipotoxicity-induced injury in diabetic kidney disease.Renal failure · 2024Article
- The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.Medicina (Kaunas, Lithuania) · 2024Review
- To target cellular senescence in diabetic kidney disease: the known and the unknown.Clinical science (London, England : 1979) · 2024Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gliflozins are a new class of antidiabetic drugs with renoprotective properties. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to high-glucose conditions in the presence or absence of dapagliflozin, we evaluated cellular senescence pathways. High glucose increased sodium-glucose cotransporter-2 (SGLT-2) expression and glucose consumption, enhancing reactive oxygen species production. The latter induced DNA damage, ataxia telangiectasia mutated kinase (ATM), and p53 phosphorylation. Stabilized p53 increased the cell cycle inhibitor p21, resulting in cell cycle arrest and increasing the cellular senescence marker beta-galactosidase (GLB-1). RPTECs under high glucose acquired a senescence-associated secretory phenotype, which was detected by the production of IL-1β, IL-8, and TGF-β1. By decreasing SGLT-2 expression and glucose consumption, dapagliflozin inhibited the above pathway and prevented RPTEC senescence. In addition, dapagliflozin reduced the cell cycle inhibitor p16 independently of the glucose conditions. Neither glucose concentration nor dapagliflozin affected the epithelial-to-mesenchymal transition when assessed with α-smooth muscle actin (α-SMA). Thus, high glucose induces p21-dependent RPTEC senescence, whereas dapagliflozin prevents it. Since cellular senescence contributes to the pathogenesis of diabetic nephropathy, delineating the related molecular mechanisms and the effects of the widely used gliflozins on them is of particular interest and may lead to novel therapeutic approaches.
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