ArticleJournal of the American Society of Nephrology : JASN2014
Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular senescence.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 116 citations in OpenAlex.
- Review
- Dendrobine ameliorates mitophagy-mediated endothelial senescence in diabetic kidney disease through activating the SIRT1/FOXO3a pathway.Chinese medicine · 2025Article
- Impacts of Radiation on Metabolism and Vascular Cell Senescence.Antioxidants & redox signaling · 2025Review
- Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury.The Journal of clinical investigation · 2025Review
- SIRT1: The first key to unlocking the mystery of cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Lumican Is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting Vascular Smooth Cells Senescence Through Interacting With Integrin α2β1.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Sirtuins in kidney health and disease.Nature reviews. Nephrology · 2024Review
- Permissive role of vascular endothelium in fibrosis: focus on the kidney.American journal of physiology. Cell physiology · 2024Review
- Sirtuins in kidney diseases: potential mechanism and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- Potential Nephroprotective Effect of Kaempferol: Biosynthesis, Mechanisms of Action, and Clinical Prospects.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Sirtuins in kidney homeostasis and disease: where are we now?Frontiers in endocrinology · 2024Review
- Early aging and premature vascular aging in chronic kidney disease.Clinical kidney journal · 2023Review
- Mitochondrial Oxidative Metabolism: An Emerging Therapeutic Target to Improve CKD Outcomes.Biomedicines · 2023Review
- Cellular senescence and the blood-brain barrier: Implications for aging and age-related diseases.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging.International journal of molecular sciences · 2022Review
- SIRT6 in Vascular Diseases, from Bench to Bedside.Aging and disease · 2022Article
- The effects of exercise on kidney injury: the role of SIRT1.Molecular biology reports · 2022Review
- Review
- Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Sirtuin 1 (SIRT1) depletion in vascular endothelial cells mediates endothelial dysfunction and premature senescence in diverse cardiovascular and renal diseases. However, the molecular mechanisms underlying these pathologic effects remain unclear. Here, we examined the phenotype of a mouse model of vascular senescence created by genetically ablating exon 4 of Sirt1 in endothelial cells (Sirt1(endo-/-)). Under basal conditions, Sirt1(endo-/-) mice showed impaired endothelium-dependent vasorelaxation and angiogenesis, and fibrosis occurred spontaneously at low levels at an early age. In contrast, induction of nephrotoxic stress (acute and chronic folic acid-induced nephropathy) in Sirt1(endo-/-) mice resulted in robust acute renal functional deterioration followed by an exaggerated fibrotic response compared with control animals. Additional studies identified matrix metalloproteinase-14 (MMP-14) as a target of SIRT1. In the kidneys of Sirt1(endo-/-) mice, impaired angiogenesis, reduced matrilytic activity, and retention of the profibrotic cleavage substrates tissue transglutaminase and endoglin accompanied MMP-14 suppression. Furthermore, restoration of MMP-14 expression in SIRT1-depeleted mice improved angiogenic and matrilytic functions of the endothelium, prevented renal dysfunction, and attenuated nephrosclerosis. Our findings establish a novel mechanistic molecular link between endothelial SIRT1 depletion, downregulation of MMP-14, and the development of nephrosclerosis.
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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.