ArticlePloS one2012
Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Everolimus-Involving Immunosuppression Attenuates Renal Interstitial Fibrosis Through Modulation of Mammalian Target of Rapamycin-Related Signal Transduction.International journal of molecular sciences · 2026Article
- Experimental rodent models of cardiorenal syndrome types 3 and 4: Insights and clinical relevance (Review).International journal of molecular medicine · 2026Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Impact of immunosuppressive therapy on pulmonary perfusion in kidney transplant recipients after COVID-19 illness.Frontiers in medicine · 2025Article
- mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis.Frontiers in pharmacology · 2021Review
- The Effects of Immunosuppressive Treatment during Pregnancy on the Levels of Potassium, Iron, Chromium, Zinc, Aluminum, Sodium and Molybdenum in Hard Tissues of Female Rats and Their Offspring.International journal of molecular sciences · 2020Article
- Preventive effect of early introduction of everolimus and reduced-exposure tacrolimus on renal interstitial fibrosis in de novo living-donor renal transplant recipients.Clinical and experimental nephrology · 2020Article
- Cyclin G1 and TASCC regulate kidney epithelial cell GScience translational medicine · 2019Article
- The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats.Apoptosis : an international journal on programmed cell death · 2016Article
- Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.Nature reviews. Nephrology · 2016Review
- The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.Drug design, development and therapy · 2016Article
- Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.BioMed research international · 2016Article
- Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo.Critical care medicine · 2015Article
- Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients.Therapeutics and clinical risk management · 2015Article
- Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients.Clinical and experimental nephrology · 2014Article
- mTOR inhibitors and renal allograft: Yin and Yang.Journal of nephrology · 2014Review
- Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation.Fibrogenesis & tissue repair · 2014Review
- Everolimus-induced epithelial to mesenchymal transition in immortalized human renal proximal tubular epithelial cells: key role of heparanase.Journal of translational medicine · 2013Article
- TGF-β/Smad3 activates mammalian target of rapamycin complex-1 to promote collagen production by increasing HIF-1α expression.American journal of physiology. Renal physiology · 2013Article
- Transforming growth factor-beta and the glomerular filtration barrier.Kidney research and clinical practice · 2013Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats.
methodsThis study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation.
resultsEverolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model.
conclusionDelayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.
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