ArticleJournal of cellular and molecular medicine2021
Deletion of Smad3 protects against diabetic myocardiopathy in db/db mice.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- From Type 2 Diabetes Mellitus To Diabetic Cardiomyopathy - A Systematic Review On The Role Of MicroRNA.Current diabetes reports · 2025Pooled it
- WTAP Deficiency Promotes Podocyte PANoptosis and FSGS via SPP1 Signaling.Circulation research · 2026Article
- Oxidative stress and ferroptosis in diabetic cardiomyopathy: mechanistic interplay and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Gene- and cell-based therapy in cardiovascular diseases.Journal of cardiovascular pharmacology · 2025Article
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions.MedComm · 2024Review
- The mechanisms and therapeutic potential of clopidogrel in mitigating diabetic cardiomyopathy in db/db mice.iScience · 2024Article
- Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.International journal of biological sciences · 2024Article
- Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Activating transcription factor 4 drives the progression of diabetic cardiac fibrosis.ESC heart failure · 2023Article
- Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db/db Mice by Targeting PPARδ.International journal of molecular sciences · 2023Article
- Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis.World journal of stem cells · 2023Article
- Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice.Journal of dental sciences · 2023Article
- Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway.Frontiers in pharmacology · 2023Review
- Review
- Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy.Frontiers in endocrinology · 2022Review
- Deletion of Smad3 protects against diabetic myocardiopathy in db/db mice.Journal of cellular and molecular medicine · 2021Article
- Inhibitory effect of microRNA-21 on pathways and mechanisms involved in cardiac fibrosis development.Therapeutic advances in cardiovascular diseaseReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Diabetic cardiomyopathy (DCM) is a common diabetic complication characterized by diastolic relaxation abnormalities, myocardial fibrosis and chronic heart failure. Although TGF-β/Smad3 signalling has been shown to play a critical role in chronic heart disease, the role and mechanisms of Smad3 in DCM remain unclear. We reported here the potential role of Smad3 in the development of DCM by genetically deleting the Smad3 gene from db/db mice. At the age of 32 weeks, Smad3WT-db/db mice developed moderate to severe DCM as demonstrated by a marked increase in the left ventricular (LV) mass, a significant fall in the LV ejection fraction (EF) and LV fractional shortening (FS), and progressive myocardial fibrosis and inflammation. In contrast, db/db mice lacking Smad3 (Smad3KO-db/db) were protected against the development of DCM with normal cardiac function and undetectable myocardial inflammation and fibrosis. Interestingly, db/db mice with deleting one copy of Smad3 (Smad3 ± db/db) did not show any cardioprotective effects. Mechanistically, we found that deletion of Smad3 from db/db mice largely protected cardiac Smad7 from Smurf2-mediated ubiquitin proteasome degradation, thereby inducing IBα to suppress NF-kB-driven cardiac inflammation. In addition, deletion of Smad3 also altered Smad3-dependent miRNAs by up-regulating cardiac miR-29b while suppressing miR-21 to exhibit the cardioprotective effect on Smad3KO-db/db mice. In conclusion, results from this study reveal that Smad3 is a key mediator in the pathogenesis of DCM. Targeting Smad3 may be a novel therapy for DCM.
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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 OpenQuestion graph.