ArticleJournal of diabetes and its complications
Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy.
Article in Journal of diabetes and its complications. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review.Journal of diabetes research · 2020Pooled it
- Natural products modulate renal metabolic reprogramming in diabetic kidney disease.Journal of translational internal medicine · 2026Article
- Targeting cellular senescence in diabetic kidney disease: potential of regenerative, cell-based therapies and other senotherapeutic approaches.Kidney international · 2026Review
- Cell Type-Specific Expression of p16, p21, and p53 Reveals Age-Dependent Glial Senescence in the AppAging cell · 2026Article
- Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026Review
- Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The SGLT2i "canagliflozin" and the DPP-4i "sitagliptin" mitigate hypertensive nephropathy in adult male rats by modulating the Ang II/RAGE/Nox4/NLRP3 cascade.Frontiers in physiology · 2026Article
- Senotherapeutics for metabolic disease and diabetic complications.Journal of internal medicine · 2026Review
- New Insights into the Role of Mitochondrial Dysfunction in Diabetic Kidney Disease in the Omics Era.Diabetes, metabolic syndrome and obesity : targets and 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
- Review
- Putrescine functions as a metabolic checkpoint in replication stress-induced senescence.Cellular and molecular life sciences : CMLS · 2025Article
- SGLT2 inhibitors as a novel senotherapeutic approach.npj aging · 2025Review
- Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.Frontiers of medicine · 2025Review
- Article
- Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- The Role of Mitochondria in Diabetic Kidney Disease and Potential Therapeutic Targets.Kidney international reports · 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
- Topical Application of miR-200b-3p by Poloxamer 407-Based Hydrogel Accelerates Diabetic Wound Healing.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsKidney cells in patients with diabetic nephropathy are reported to be senescent. However, the mechanisms that regulate cellular senescence in the diabetic kidney are still unknown. In the present study, we evaluated the contribution of high glucose to renal cell senescence in streptozotocin (STZ)-induced diabetic mice.
methodsNon-diabetic and streptozotocin (STZ, 10mgkg(-1)day(-1) for 7days, i.p.)-induced type 1 diabetic C57BL/6J mice and cultured human proximal tubular cells were used in this study.
resultsHyperglycemia dramatically increased the renal expression of p21 but not other CDK inhibitors such as p16 and p27 at 4weeks after STZ injection. These changes were accompanied by an increase in senescence-associated β-galactosidase staining in tubular epithelial cells. Administration of insulin at doses that maintained normoglycemia or mild hypoglycemia suppressed the changes induced by STZ. Insulin did not affect the senescent markers in non-diabetic mice. Exposure of cultured human proximal tubular cells to 25mmol/L, but not 8mmol/L, glucose medium increased the expression of senescence markers, which was suppressed by knock-down of p21 or sodium glucose cotransporter (SGLT) 2.
conclusionsThese results suggest that hyperglycemia causes tubular senescence via a SGLT2- and p21-dependent pathway in the type 1 diabetic kidney.
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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.