ArticleScientific reports2019
Hypoxia-inducible factor-1α is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Application of SGLT2 inhibitors in kidney diseases: a bibliometric analysis.Frontiers in medicine · 2026Pooled it
- Effect of sodium-glucose cotransporter 2 inhibitors on hemoglobin and hematocrit levels in type 2 diabetes: a systematic review and meta-analysis.International urology and nephrology · 2022Pooled it
- How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD.Hepatology communications · 2022Trial
- Linagliptin increases the expression of LRP2 independent of Nrf2 in streptozotocin-induced diabetic mice.Journal of diabetes investigation · 2026Article
- Empagliflozin modulates microRNA expression in human primary cardiomyocytes under CoClInternational journal of cardiology. Cardiovascular risk and prevention · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- The SGLT2 Inhibitor Canagliflozin Promotes β-Cell Regeneration and Restores and Stabilises β-Cell Identity in a Polygenic Model of Severe Early-Onset Type 2 Diabetes.Journal of cellular and molecular medicine · 2026Article
- Modified Shen-Yan-Fang-Shuai formula attenuates diabetic kidney disease progression via regulation of HIF-1α-mediated mitochondrial energy metabolism.Chinese medicine · 2026Article
- Findings Interpretation Concerns Regarding the Emulated Target Trial of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Psoriatic Arthritis [Letter].Drug design, development and therapy · 2026Article
- Canagliflozin ameliorates high-salt-induced renal injury and premature aging in male Dahl salt-sensitive rats, with associated changes in SIRT6/HIF-1α signaling.Renal failure · 2025Article
- Canagliflozin improves high-salt-induced aortic arteriosclerosis and premature aging in dahl salt-sensitive rats through the SIRT6/HIF-1 α signaling pathway.Molecular and cellular biochemistry · 2025Article
- Coordinated expression of BMP10/ALK1/endoglin-proteins that drive embryonic cardiac and vascular morphogenesis-in patients with heart failure: The EMPEROR Program.European journal of heart failure · 2025Article
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- Blood Pressure Management Strategies and Podocyte Health.American journal of hypertension · 2025Review
- Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?Journal of veterinary pharmacology and therapeutics · 2025Review
- Qi-Gui-Sheng-Jiang-San Decoction Regulating Hypoxia Response Through Non-Oxygen-Dependent Pathway Improves Diabetic Kidney Disease: Coupling Network Pharmacology With Experimental Verification.Journal of diabetes research · 2025Article
- Immune-metabolic interactions shape the fibrotic landscape of diabetic kidney disease: emerging mechanisms and therapeutic prospects.Frontiers in physiology · 2025Review
- SGLT2 inhibitors as metabolic modulators: beyond glycemic control in type 2 diabetes.Frontiers in endocrinology · 2025Review
- Advances in kidney disease: pathogenesis and therapeutic targets.Frontiers in medicine · 2025Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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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
Previous studies have demonstrated intrarenal hypoxia in patients with diabetes. Hypoxia-inducible factor (HIF)-1 plays an important role in hypoxia-induced tubulointerstitial fibrosis. Recent clinical trials have confirmed the renoprotective action of SGLT2 inhibitors in diabetic nephropathy. We explored the effects of an SGLT2 inhibitor, luseogliflozin on HIF-1α expression in human renal proximal tubular epithelial cells (HRPTECs). Luseogliflozin significantly inhibited hypoxia-induced HIF-1α protein expression in HRPTECs. In addition, luseogliflozin inhibited hypoxia-induced the expression of the HIF-1α target genes PAI-1, VEGF, GLUT1, HK2 and PKM. Although luseogliflozin increased phosphorylated-AMP-activated protein kinase α (p-AMPKα) levels, the AMPK activator AICAR did not changed hypoxia-induced HIF-1α expression. Luseogliflozin suppressed the oxygen consumption rate in HRPTECs, and subsequently decreased hypoxia-sensitive dye, pimonidazole staining under hypoxia, suggesting that luseogliflozin promoted the degradation of HIF-1α protein by redistribution of intracellular oxygen. To confirm the inhibitory effect of luseogliflozin on hypoxia-induced HIF-1α protein in vivo, we treated male diabetic db/db mice with luseogliflozin for 8 to 16 weeks. Luseogliflozin attenuated cortical tubular HIF-1α expression, tubular injury and interstitial fibronectin in db/db mice. Together, luseogliflozin inhibits hypoxia-induced HIF-1α accumulation by suppressing mitochondrial oxygen consumption. The SGLT2 inhibitors may protect diabetic kidneys by therapeutically targeting HIF-1α protein.
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