ArticleEndocrinology and metabolism (Seoul, Korea)2022
EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation.
Article in Endocrinology and metabolism (Seoul, Korea), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Abrine targets ERK to suppress EMT and lung metastasis model via MAPKs and Nrf2/Keap-1/HO-1 signaling.Frontiers in immunology · 2026Article
- Combination of THU/ALK-5i exhibits profound anti-MASH activity through suppression of lipogenesis and fibrogenesis.Scientific reports · 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
- Targeting endoplasmic reticulum stress: an innovative therapeutic strategy for podocyte-related kidney diseases.Journal of translational medicine · 2025Review
- Mesangial Cells in Diabetic Kidney Disease: From Mechanisms to Therapeutic Implications.International journal of biological sciences · 2025Review
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.Biomolecules · 2024Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis.Diabetes & metabolism journal · 2023Article
- Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells.
methodsIn vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated.
resultsEnhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells.
conclusionEW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.
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