ArticleClinical science (London, England : 1979)2021
Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice.
Article in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Comprehensive evaluation of GLP-1 receptor agonists: an umbrella review of clinical outcomes across multiple diseases.Nature communications · 2026Pooled it
- Effect of dapagliflozin on the initial estimated glomerular filtration rate dip in chronic kidney disease patients without diabetes mellitus.Clinical and experimental nephrology · 2023Trial
- Article
- Mas-related G protein-coupled receptor type D deficiency promotes tubulointerstitial injury and fibrosis associated with proteinuria in male mice.Physiological reports · 2026Article
- Chronic Kidney Disease in Metabolic Disease: Regulation of SGLT2 and Transcriptomic-Epigenetic Effects of Its Pharmacological Inhibition.International journal of molecular sciences · 2026Review
- Chronic cardiorenal syndrome: cardio-renal protective effect of SGLT2i.Renal failure · 2025Review
- Assessment of protective effect of the losartan against cisplatin-induced nephrotoxicity in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- When the Heart Hurts the Kidneys: From Flow to Translational Future.Seminars in nephrology · 2025Review
- Tubular Injury in Diabetic Kidney Disease: Early Diagnosis and Intervention Strategies.Diabetes/metabolism research and reviews · 2025Review
- Dapagliflozin, in addition to ramipril, ameliorates kidney disease progression in mice with Alport syndrome.American journal of physiology. Renal physiology · 2025Article
- Atrial Cardiomyopathy in Atrial Fibrillation: Mechanistic Pathways and Emerging Treatment Concepts.Journal of clinical medicine · 2025Review
- Article
- The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure.Biomedicines · 2025Review
- Effects of sodium/glucose cotransporter 2 inhibitors on the coagulation profile in patients with coronary-artery disease and type 2 diabetes mellitus: a retrospective cohort study.Frontiers in cardiovascular medicine · 2025Article
- Application of SGLT-2 inhibitors in non-diabetic CKD: mechanisms, efficacy, and safety.Frontiers in medicine · 2025Review
- Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets.International journal of molecular sciences · 2024Review
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- Research progress on the effects of sodium-glucose linked transporter 2 inhibitors on multiple metabolic disorders in metabolic syndrome.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.Cardiovascular research · 2024Review
- SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway.Diabetology & metabolic syndrome · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Clinical trials indicate that sodium/glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) improve kidney function, yet, the molecular regulation of SGLT2 expression is incompletely understood. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) on SGLT2 expression. In adult non-diabetic participants in the Nephrotic Syndrome Study Network (NEPTUNE, n=163), multivariable linear regression analysis showed SGLT2 mRNA was significantly associated with angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE) mRNA levels (P<0.001). In vitro, angiotensin II (Ang II) dose-dependently stimulated SGLT2 expression in HK-2, human immortalized renal proximal tubular cells (RPTCs); losartan and antioxidants inhibited it. Sglt2 expression was increased in transgenic (Tg) mice specifically overexpressing Agt in their RPTCs, as well as in WT mice with a single subcutaneous injection of Ang II (1.44 mg/kg). Moreover, Ang II (1000 ng/kg/min) infusion via osmotic mini-pump in WT mice for 4 weeks increased systolic blood pressure (SBP), glomerulosclerosis, tubulointerstitial fibrosis, and albuminuria; canaglifozin (Cana, 15 mg/kg/day) reversed these changes, with the exception of SBP. Fractional glucose excretion (FeGlu) was higher in Ang II+Cana than WT+Cana, whereas Sglt2 expression was similar. Our data demonstrate a link between intrarenal RAS and SGLT2 expression and that SGLT2i ameliorates Ang II-induced renal injury independent of SBP.
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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 Socratic graph.