ArticleFEBS open bio2021
Dapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immunometabolic Effects of SGLT2 Inhibitors on the Th17/Treg Axis: Mechanisms, Evidence, and Implications for Therapeutic Repurposing.Molecular biology reports · 2026Review
- Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart Failure-A Subanalysis of the ERASe Trial.Journal of clinical medicine · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Role of Treg cells in diabetes mellitus and association with traditional Chinese medicine: a literature review.Frontiers in immunology · 2026Review
- CD4Frontiers in immunology · 2026Review
- MIF Regulates the Th17/Treg Ratio to Exacerbate Kidney Injury in Chronic Kidney Disease.Inflammation · 2025Article
- Sodium-glucose cotransporter-2 inhibitors and risk of autoimmune rheumatic diseases: population based cohort study.BMJ (Clinical research ed.) · 2025Article
- Canagliflozin Inhibits Electrogenic Na+ Transport in Mouse Cortical Collecting Duct Cells.Function (Oxford, England) · 2025Article
- Potential Role of SGLT-2 Inhibitors in Improving Allograft Function and Reducing Rejection in Kidney Transplantation.Clinical transplantation · 2025Review
- Effects of empagliflozin on interleukin-23 secretion from peripheral blood mononuclear cells in patients with type 2 diabetes versus healthy subjects: an in vitro study.Molecular biology reports · 2025Article
- SGLT2 Inhibitors in Glomerulonephritis: Beyond Nephroprotection?Journal of clinical medicine · 2025Review
- Unraveling the Potential of SGK1 in Osteoporosis: From Molecular Mechanisms to Therapeutic Targets.Biomolecules · 2025Review
- Exploring the interplay between adipokine-mediated celastrol target genes and T cells in diabetic nephropathy: a mendelian randomization-based causal inference.Diabetology & metabolic syndrome · 2025Article
- Cardiac Fibrosis: Mechanistic Discoveries Linked to SGLT2 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Emerging role of adaptive immunity in diabetes-induced cognitive impairment: from the periphery to the brain.Metabolic brain disease · 2025Review
- SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges.Frontiers in immunology · 2025Review
- Heat shock protein 70 promotes the progression of type 2 diabetic nephropathy by inhibiting T-cell immunoglobulin and mucin domain-3 and thereby promoting Th17/Treg imbalance.Nephrology (Carlton, Vic.) · 2024Article
- Impact of hyperglycemia on immune cell function: a comprehensive review.Diabetology international · 2024Review
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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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
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
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