ArticleCellular signalling2020
Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition.
Article in Cellular signalling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Refractory IgA Nephropathy: A Challenge for Future Nephrologists.Medicina (Kaunas, Lithuania) · 2024Pooled it
- LncPTEC mediated homocysteine accumulation elevates oxidative stress via UBQLN1-dependent MTHFD1 ubiquitination in DKD.Cell death & disease · 2026Article
- Acute vascular redox modulation by SGLT2 inhibition in non-diabetic patients.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- The Roles of the Membrane-Anchored Glycoprotein RECK in Animal Development, Tumor Suppression, and Beyond.Life (Basel, Switzerland) · 2026Review
- Empagliflozin Alleviates Changes in Renal Expression of E- and N-Cadherins in Mice with Type 2 Diabetes Mellitus.Bulletin of experimental biology and medicine · 2026Article
- Non-Coding RNA in Type 2 Diabetes Cardio-Renal Complications and SGLT2 Inhibitor Response.International journal of molecular sciences · 2025Review
- Investigating the Role of Empagliflozin in the Pathological Progress of Ischemia-Reperfusion Injury in Rat Kidneys: The Involvement of Nitric Oxide.Advanced pharmaceutical bulletin · 2025Article
- Sodium-Glucose Cotransporter-2 Inhibitors in Diabetes and Beyond: Mechanisms, Pleiotropic Benefits, and Clinical Use-Reviewing Protective Effects Exceeding Glycemic Control.Molecules (Basel, Switzerland) · 2025Review
- Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells.Journal of translational medicine · 2025Article
- Empagliflozin alleviates type 2 diabetic renal fibrosis by inhibiting SLC7A7-mediated ferroptosis.Diabetology & metabolic syndrome · 2025Article
- Empagliflozin targeted the immune-related gene PIK3CA in type 2 diabetes mellitus treatment: network pharmacology analysis and experimental evidence.Diabetology & metabolic syndrome · 2025Article
- Evaluation of the novel ALK5 inhibitor EW-7197 on therapeutic efficacy in renal fibrosis using a three-dimensional chip model.Kidney research and clinical practice · 2025Article
- Review
- Study on effect of pancreatic kininogenase on diabetic nephropathy-induced fibrosis via Notch1/Hes1/Pten/Akt signaling pathway.BMC nephrology · 2025Article
- MiR-192-5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3.Non-coding RNA research · 2025Article
- Sodium-Glucose Cotransporter 2 Inhibitors as Potential Antioxidant Therapeutic Agents in Cardiovascular and Renal Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Anti-Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages.International journal of molecular sciences · 2025Review
- Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy.Redox report : communications in free radical research · 2024Review
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Proximal tubular epithelial cells (PTEC) in the S1 segment of the kidney abundantly express sodium-glucose co-transporters (SGLT) that play a critical role in whole body glucose homeostasis. We recently reported suppression of RECK (Reversion Inducing Cysteine Rich Protein with Kazal Motifs), a membrane anchored endogenous MMP inhibitor and anti-fibrotic mediator, in the kidneys of db/db mice, a model of diabetic kidney disease (DKD), as well as in high glucose (HG) treated human kidney proximal tubule cells (HK-2). We further demonstrated that empagliflozin (EMPA), an SGLT2 inhibitor, reversed these effects. Little is known regarding the mechanisms underlying RECK suppression under hyperglycemic conditions, and its rescue by EMPA. Consistent with our previous studies, HG (25 mM) suppressed RECK expression in HK-2 cells. Further mechanistic investigations revealed that HG induced superoxide and hydrogen peroxide generation, oxidative stress-dependent TRAF3IP2 upregulation, NF-κB and p38 MAPK activation, inflammatory cytokine expression (IL-1β, IL-6, TNF-α, and MCP-1), miR-21 induction, MMP2 activation, and RECK suppression. Moreover, RECK gain-of-function inhibited HG-induced MMP2 activation and HK-2 cell migration. Similar to HG, advanced glycation end products (AGE) induced TRAF3IP2 and suppressed RECK, effects that were inhibited by EMPA. Importantly, EMPA treatment ameliorated all of these deleterious effects, and inhibited epithelial-to-mesenchymal transition (EMT) and HK-2 cell migration. Collectively, these findings indicate that hyperglycemia and associated AGE suppress RECK expression via oxidative stress/TRAF3IP2/NF-κB and p38 MAPK/miR-21 induction. Furthermore, these results suggest that interventions aimed at restoring RECK or inhibiting SGLT2 have the potential to treat kidney inflammatory response/fibrosis and nephropathy under chronic hyperglycemic conditions, such as DKD.
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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.