ArticleDiabetes2010
Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
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Who cites it
159 citing papers in PubMed, 250 citations in OpenAlex.
- Wound Healing and Angiogenic Profiling of Dermal Endothelial Cells Isolated From People With Type 2 Diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- PLCε regulates podocyte differentiation and TGF-β1 responses via alteration of SMAD2/SMAD3 ratio.Cell communication and signaling : CCS · 2026Article
- Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a narrative review.Cardiovascular diagnosis and therapy · 2026Review
- The role of the vascular niche in regulating kidney tubulointerstitial fibrosis.Kidney international · 2026Review
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- A Narrative Review of Salivary Gland Extracellular Matrix and Sjögren's Syndrome: Research Status and Future Prospects.Biomolecules · 2026Review
- Endothelial to mesenchymal transition: a central mechanism in diabetes-induced vascular pathology.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Role of the TGF‑β/Smad signaling pathway in the transition from acute kidney injury to chronic kidney disease (Review).International journal of molecular medicine · 2025Review
- Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3.The world journal of men's health · 2025Article
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Identifying pathways to cardiovascular mortality by causal graphical models and mediation analysis among hypertensive patients: insights from a prospective study.Journal of translational medicine · 2025Article
- Adenosine ACells · 2025Article
- From fat to filter: the effect of adipose tissue-derived signals on kidney function.Nature reviews. Nephrology · 2025Review
- Nephrectomy Induces Severe Bone Loss in Mice Expressing Constitutively Active TGFβ Receptor Type I.International journal of molecular sciences · 2025Article
- MiR-23b-3p ameliorates sepsis-induced acute lung injury by inhibiting SMAD3-mediated endothelial-mesenchymal transition.Burns & trauma · 2025Article
- The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment.Frontiers in oncology · 2025Review
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- Linc-ROR Modulates the Endothelial-Mesenchymal Transition of Endothelial Progenitor Cells through the miR-145/Smad3 Signaling Pathway.Physiological research · 2024Article
- Sirt7/HIC1 complex participates in hyperglycaemia-mediated EndMT via modulation of SDC1 expression in diabetic kidney disease and metabolic memory.Journal of cellular and molecular medicine · 2024Article
- Knocking out USP7 attenuates cardiac fibrosis and endothelial-to-mesenchymal transition by destabilizing SMAD3 in mice with heart failure with preserved ejection fraction.Theranostics · 2024Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveA multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND
methodsEndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice.
resultsConfocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy.
conclusionsEndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications.
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