ArticlePloS one2013
Simvastatin alleviates hyperpermeability of glomerular endothelial cells in early-stage diabetic nephropathy by inhibition of RhoA/ROCK1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Association between the oxidative balance score and diabetic kidney disease in diabetes mellitus patients: insights from NHANES 2011-2018.Frontiers in nutrition · 2025Article
- Renal protective potential of pentoxifylline, chlorpromazine, and lovastatin in ischemia-reperfusion injury: An experimental study.PloS one · 2024Article
- Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review.World journal of diabetes · 2023Review
- Simvastatin Improves Outcomes of Endotoxin-induced Coagulopathy by Regulating Intestinal Microenvironment.Current medical science · 2022Article
- LncRNA ZFAS1 regulates the proliferation, oxidative stress, fibrosis, and inflammation of high glucose-induced human mesangial cells via the miR-588/ROCK1 axis.Diabetology & metabolic syndrome · 2022Article
- S-Nitrosylation of RhoGAP Myosin9A Is Altered in Advanced Diabetic Kidney Disease.Frontiers in medicine · 2021Article
- Simvastatin improves lysosome function via enhancing lysosome biogenesis in endothelial cells.Frontiers in bioscience (Landmark edition) · 2020Article
- New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism.Diabetologia · 2019Review
- A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier.Nature communications · 2019Article
- Protective effects of lycium barbarum polysaccharides on blood-retinal barrier via ROCK1 pathway in diabetic rats.American journal of translational research · 2019Article
- A Positive Feedback Loop of Profilin-1 and RhoA/ROCK1 Promotes Endothelial Dysfunction and Oxidative Stress.Oxidative medicine and cellular longevity · 2018Article
- Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells.Journal of cellular physiology · 2018Article
- QiDiTangShen Granules Reduced Diabetic Kidney Injury by Regulating the Phosphorylation Balance of the Tyrosine and Serine Residues of Insulin Receptor Substrate 1.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats.Molecular medicine reports · 2017Article
- Endothelial barrier protective properties of low molecular weight heparin: A novel potential tool in the prevention of cancer metastasis?Research and practice in thrombosis and haemostasis · 2017Article
- Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling.Frontiers in pharmacology · 2017Article
- The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA.mBio · 2016Article
- ROCK1 Induces Endothelial-to-Mesenchymal Transition in Glomeruli to Aggravate Albuminuria in Diabetic Nephropathy.Scientific reports · 2016Article
- CKD Stimulates Muscle Protein Loss Via Rho-associated Protein Kinase 1 Activation.Journal of the American Society of Nephrology : JASN · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy (DN). There is increasing evidence that dysfunction of the endothelial tight junction is a crucial step in the development of endothelial hyperpermeability, but it is unknown whether this occurs in glomerular endothelial cells (GEnCs) during the progression of DN. We examined tight junction dysfunction of GEnCs during early-stage DN and the potential underlying mechanisms. We also examined the effect of simvastatin (3-Hydroxy-3-methylglutaryl CoA reductase inhibitor) on dysfunction of the tight junctions of cultured GEnCs and in db/db mice with early-stage DN.
methodsWe assessed the expression of occludin and ZO-1, two major components of the tight junction complex, in cultured rat GEnCs treated with high glucose and in 12 week-old db/db mice with early-stage DN. We also investigated activation of RhoA/ROCK1 signaling, GEnC permeability, and renal function of the mice.
resultsHigh glucose suppresses occludin expression and disrupts occludin/ZO-1 translocation in GEnCs. These changes were associated with increased permeability to albumin and activation of RhoA/ROCK1 signaling. Occludin and ZO-1 dysregulation also occurred in the glomeruli of mice with early-stage DN, and these abnormalities were accompanied by albuminuria and activation of RhoA/ROCK1 in isolated glomeruli. Simvastatin prevented high glucose or hyperglycemia-induced dysregulation of occludin and ZO-1 by inhibition of RhoA/ROCK1 signaling in cultured GEnCs and in db/db mice with early-stage DN.
conclusionOur results indicate that activation of RhoA/ROCK1 by high glucose disrupts the expression and translocation of occludin/ZO-1 and that simvastatin alleviates occludin/ZO-1 dysregulation and albuminuria by suppressing RhoA/ROCK1 signaling during early-stage DN. These results suggest a potential therapeutic strategy for preventing the onset of albuminuria in early-stage DN.
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