ArticleJournal of the American Society of Nephrology : JASN2015
Curtailing endothelial TGF-β signaling is sufficient to reduce endothelial-mesenchymal transition and fibrosis in CKD.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- A systematic review and meta-analysis of cell-based interventions in experimental diabetic kidney disease.Stem cells translational medicine · 2021Pooled it
- Transforming growth factor-β in kidney disease in dogs and cats: a review of the evidence of its role in renal fibrosis.Journal of veterinary internal medicine · 2026Review
- The endothelium response to kidney injury.Nature reviews. Nephrology · 2026Review
- Establishment and characterization of a rat model of ureteral scar stricture induced by mechanical injury.International urology and nephrology · 2026Article
- Vascular transcriptional and metabolic changes precede progressive intrarenal microvascular rarefaction in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2026Article
- TNFα and Endothelial IL-1 Receptor Signaling Drive Peritubular Capillary Regression and Fibrosis in Obstructive Kidney Injury.bioRxiv : the preprint server for biology · 2025Article
- Sustained mesenchymal reprogramming of endothelial cells after completion of chemotherapy.Cardio-oncology (London, England) · 2025Article
- Tracing the origin of myofibroblasts in kidney fibrosis.Nature communications · 2025Article
- New and Emerging Biomarkers in Chronic Kidney Disease.Biomedicines · 2025Review
- Association of thrombomodulin with the severity of chronic kidney disease: a cross-sectional study.BMC nephrology · 2025Article
- Molecular mechanisms of endothelial-mesenchymal transition and its pathophysiological feature in cerebrovascular disease.Cell & bioscience · 2025Review
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- CD146⁺ Endothelial Cells Facilitate Renal Interstitial Fibrosis Through Endothelial-to-Mesenchymal Transition.Annals of transplantation · 2024Article
- Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres.Experimental & molecular medicine · 2024Article
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- Midkine promotes renal fibrosis by stabilizing C/EBPβ to facilitate endothelial-mesenchymal transition.Communications biology · 2024Article
- Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease.Cardiovascular research · 2024Review
- Permissive role of vascular endothelium in fibrosis: focus on the kidney.American journal of physiology. Cell physiology · 2024Review
- Article
- MircroRNA-92b as a negative regulator of the TGF-β signaling by targeting the type I receptor.iScience · 2023Article
38 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
Excessive TGF-β signaling in epithelial cells, pericytes, or fibroblasts has been implicated in CKD. This list has recently been joined by endothelial cells (ECs) undergoing mesenchymal transition. Although several studies focused on the effects of ablating epithelial or fibroblast TGF-β signaling on development of fibrosis, there is a lack of information on ablating TGF-β signaling in the endothelium because this ablation causes embryonic lethality. We generated endothelium-specific heterozygous TGF-β receptor knockout (TβRII(endo+/-)) mice to explore whether curtailed TGF-β signaling significantly modifies nephrosclerosis. These mice developed normally, but showed enhanced angiogenic potential compared with TβRII(endo+/+) mice under basal conditions. After induction of folic acid nephropathy or unilateral ureteral obstruction, TβRII(endo+/-) mice exhibited less tubulointerstitial fibrosis, enhanced preservation of renal microvasculature, improvement in renal blood flow, and less tissue hypoxia than TβRII(endo+/+) counterparts. In addition, partial deletion of TβRII in the endothelium reduced endothelial-to-mesenchymal transition (EndoMT). TGF-β-induced canonical Smad2 signaling was reduced in TβRII(+/-) ECs; however, activin receptor-like kinase 1 (ALK1)-mediated Smad1/5 phosphorylation in TβRII(+/-) ECs remained unaffected. Furthermore, the S-endoglin/L-endoglin mRNA expression ratio was significantly lower in TβRII(+/-) ECs compared with TβRII(+/+) ECs. These observations support the hypothesis that EndoMT contributes to renal fibrosis and curtailing endothelial TGF-β signals favors Smad1/5 proangiogenic programs and dictates increased angiogenic responses. Our data implicate endothelial TGF-β signaling and EndoMT in regulating angiogenic and fibrotic responses to injury.
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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 OpenQuestion graph.