ArticleDiabetologia2012
Kidney-targeting Smad7 gene transfer inhibits renal TGF-β/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 117 citations in OpenAlex.
- MicroRNA-21 in glomerular injury.Journal of the American Society of Nephrology : JASN · 2015Trial
- miR-29b as an Anti-Fibrotic Therapeutic: Mechanisms, Disease Biology and Translational Opportunities.Cells · 2026Review
- Uncovering key markers and therapeutic targets for renal fibrosis in diabetic kidney disease through bulk and single-cell RNA sequencing.Journal of translational medicine · 2025Article
- Stroke-Induced Renal Dysfunction: Underlying Mechanisms and Challenges of the Brain-Kidney Axis.CNS neuroscience & therapeutics · 2024Review
- Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.Molecular biology reports · 2024Article
- Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Article
- Dapagliflozin can alleviate renal fibrosis in rats with streptozotocin‑induced type 2 diabetes mellitus.Experimental and therapeutic medicine · 2023Article
- Astrocyte-derived exosomal lncRNA 4933431K23Rik modulates microglial phenotype and improves post-traumatic recovery via SMAD7 regulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Effect of Moderate Intensity Continuous Training and Slow Type Interval Training to Gene Expression of TGF-β in Type 2 Diabetes Mellitus Model Wistar Rats.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2023Article
- Does hand stiffness reflect internal organ fibrosis in diabetes mellitus?Frontiers in clinical diabetes and healthcare · 2023Article
- Galaxaura elongata Extract (GE) Modulates Vanadyl Sulfate-Induced Renal Damage via Regulating TGF-β/Smads and Nrf2/NF-κB Pathways.Biological trace element research · 2022Article
- MicroRNA-10a/b inhibit TGF-β/Smad-induced renal fibrosis by targeting TGF-β receptor 1 in diabetic kidney disease.Molecular therapy. Nucleic acids · 2022Article
- Protective antioxidative and anti-inflammatory actions of β-caryophyllene against sulfasalazine-induced nephrotoxicity in rat.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- The effects of two different dietary regimens during exercise on outcome of experimental acute kidney injury.Journal of inflammation (London, England) · 2022Article
- Smad3 Signatures in Renal Inflammation and Fibrosis.International journal of biological sciences · 2022Review
- AANG Prevents Smad3-dependent Diabetic Nephropathy by Restoring Pancreatic β-Cell Development in db/db Mice.International journal of biological sciences · 2022Article
- miR-29c Inhibits Renal Interstitial Fibrotic Proliferative Properties through PI3K-AKT Pathway.Applied bionics and biomechanics · 2022Article
- Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification.Journal of immunology research · 2022Article
- A Glimpse of Inflammation and Anti-Inflammation Therapy in Diabetic Kidney Disease.Frontiers in physiology · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe TGF-β/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes.
methodsWe delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-β/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated.
resultsIn this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-β/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/
interpretationOur results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-β/SMAD and NF-κB signalling pathways.
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