ArticleProceedings of the National Academy of Sciences of the United States of America2002
3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 231 citations in OpenAlex.
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Rho/ROCK Signaling Pathway in Kidney Diseases: Mechanisms and Therapeutic Perspectives.Biomedicines · 2026Review
- Simvastatin-loaded liposomal nanoparticles as treatment for adenomyosis in a patient-derived xenograft mouse model: a pilot study.Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology · 2025Article
- Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth.International journal of molecular sciences · 2025Review
- Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway.Journal of molecular histology · 2024Article
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- Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection.Reviews in medical virology · 2023Review
- Circ_0000064 knockdown attenuates high glucose-induced proliferation, inflammation and extracellular matrix deposition of mesangial cells through miR-424-5p-mediated WNT2B inhibition in cell models of diabetic nephropathy.Clinical and experimental nephrology · 2022Article
- Dietary patterns in association with the expression of pro-metastatic genes in primary breast cancer.European journal of nutrition · 2022Article
- Rho GTPases in kidney physiology and diseases.Small GTPases · 2022Article
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Cell Cycle Dysregulation and Renal Fibrosis.Frontiers in cell and developmental biology · 2021Review
- Identification of C3 as a therapeutic target for diabetic nephropathy by bioinformatics analysis.Scientific reports · 2020Article
- miR-181a-5p regulates the proliferation and apoptosis of glomerular mesangial cells by targeting KLF6.Experimental and therapeutic medicine · 2020Article
- The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease.Journal of the Endocrine Society · 2020Review
- Cell cycle regulation and anticancer drug discovery.Cancer biology & medicine · 2017Article
- Effects of Dangguibuxue decoction on rat glomerular mesangial cells cultured under high glucose conditions.BMC complementary and alternative medicine · 2017Article
- Protective Effects of Pyridoxamine Supplementation in the Early Stages of Diet-Induced Kidney Dysfunction.BioMed research international · 2017Article
- Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling.BioMed research international · 2017Article
- Greater efficacy of atorvastatin versus a non-statin lipid-lowering agent against renal injury: potential role as a histone deacetylase inhibitor.Scientific reports · 2016Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, also known as statins, are lipid-lowering agents widely used in the prevention of coronary heart disease. Recent experimental and clinical data, however, indicate that the overall benefits of statin therapy may exceed its cholesterol-lowering properties. We postulate that statins may ameliorate the detrimental effects of high glucose (HG)-induced proliferation of mesangial cells (MCs), a feature of early stages of diabetic nephropathy, by preventing Rho isoprenylation. Rat MCs cultured in HG milieu were treated with and without simvastatin, an HMG-CoA reductase inhibitor. Simvastatin inhibited HG-induced MC proliferation as measured by [(3)H]thymidine incorporation. This inhibitory effect was reversed with geranylgeranyl pyrophosphate, an isoprenoid intermediate of the cholesterol biosynthetic pathway. At the cell-cycle level, the HG-induced proliferation of MCs was associated with a decrease in cyclin dependent kinase (CDK) inhibitor p21 protein expression accompanied by an increase in CDK4 and CDK2 kinase activities. Simvastatin reversed the down-regulation of p21 protein expression and decreased CDK4 and CDK2 kinase activities. Exposure of MCs to HG was associated with an increase in membrane-associated Ras and Rho GTPase protein expression. Cotreatment of MCs with simvastatin reversed HG-induced Ras and Rho membrane translocation. Immunofluorescence microscopy revealed that the overexpression of the dominant-negative RhoA led to a significant increase in p21 expression. Our data suggest that simvastatin represses the HG-induced Rho GTPase/p21 signaling in glomerular MCs. Thus, this study provides a molecular basis for the use of statins, independently of their cholesterol-lowering effect, in early stages of diabetic nephropathy.
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