ArticleInternational journal of biological sciences2024
Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 13 citations in OpenAlex.
- Gut microbiota and renal fibrosis: novel mechanistic insights and therapeutic potential.Acta pharmacologica Sinica · 2026Review
- Paraxanthine and azilsartan attenuate gentamicin-induced renal fibrosis via modulation of TGF-β1/Smad3/7 signaling and miRNA-21/miRNA-200b expression.Journal of translational medicine · 2026Article
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- Cinnamophilin ameliorates testosterone-induced prostatic hyperplasia and fibrosis by regulating 5α-reductase and TGF-β/Smad signaling pathway.Iranian journal of basic medical sciences · 2026Article
- Tripterygium glycosides: recent advances in mechanisms, therapeutic applications, and safety optimization.Frontiers in medicine · 2026Review
- TangShenWeiNing formula alleviates diabetic kidney disease by inhibiting ferroptosis via AMPK pathway in renal tubular epithelial cells.Frontiers in endocrinology · 2026Article
- Dapagliflozin attenuates diabetic renal fibrosis by inhibiting macrophage-myofibroblast transitionPeerJ · 2026Article
- [Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Targeted Delivery of Triptolide Alleviates Diabetic Nephropathy via Inactivation of JAK2-STAT1 Signaling.Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Prognostic value of microRNA-495-3p, adiponectin, and cardiometabolic index in type 2 diabetic nephropathy.World journal of diabetes · 2025Article
- Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights.Diabetology & metabolic syndrome · 2025Review
- Effect of resveratrol on key signaling pathways including SIRT1/AMPK/Smad3/TGF-β and miRNA-141 related to NAFLD in an animal model.Research in pharmaceutical sciences · 2025Article
- Smad3 Mediates Renal Fibrosis via GPX4-Dependent Ferroptosis.International journal of biological sciences · 2025Article
- Efficacy and safety of Guben Tongluo formula in treating chronic kidney disease (stage G3): a multicenter randomized controlled clinical trial.Frontiers in medicine · 2025Article
- Molecular mechanisms and multi-target therapeutic strategies of diabetic nephropathy: from pathogenesis to precision interventions.Frontiers in pharmacology · 2025Review
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment.Frontiers in oncology · 2025Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- FBXW7 Protects against Diabetic Nephropathy by Targeting Metadherin for Ubiquitin Degradation.Kidney diseases (Basel, Switzerland)Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β/Smad3 signaling plays a critical role in type 2 diabetes (T2D) and type 2 diabetic nephropathy (T2DN), but treatment by specifically targeting Smad3 remains unexplored. To develop a new Smad3-targeted therapy for T2D and T2DN, we treated db/db mice at the pre-diabetic or established diabetic stage with a pharmacological Smad3 inhibitor SIS3. The therapeutic effect and mechanisms of anti-Smad3 treatment on T2D and T2DN were investigated. We found that anti-Smad3 treatment on pre-diabetic db/db mice largely attenuated both T2D and T2DN by markedly reducing blood glucose levels, and inhibiting the elevated serum creatinine, microalbuminuria, and renal fibrosis and inflammation. Unexpectedly, although SIS3 treatment on the established diabetic db/db mice inhibited T2DN but did not significantly improve T2D. Mechanistically, we uncovered that inhibition of T2DN in SIS3-treated db/db mice was associated with effectively restoring the balance of TGF-β/Smad signaling by inhibiting Smad3 while increasing Smad7, thereby suppressing Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation via lncRNA Erbb4-IR and LRN9884-dependent mechanisms. We also revealed that inhibition of islet β cell injury by preventing the loss of islet Pax 6 could be the mechanism through which the pre-diabetic treatment, rather than the late SIS3 treatment on db/db mice significantly improved the T2D phenotype.
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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.