Renoprotective Effects of Atorvastatin in Diabetic Mice: Downregulation of RhoA and Upregulation of Akt/GSK3

• Published in: PloS one 2016-09, Vol.11 (9), p.e0162731
• Main Authors: Bruder-Nascimento, Thiago, Callera, Glaucia, Montezano, Augusto Cesar, Antunes, Tayze T, He, Ying, Cat, Aurelie Nguyen Dinh, Ferreira, Nathanne S, Barreto, Pedro A, Olivon, Vânia C, Tostes, Rita C, Touyz, Rhian M
• Format: Article
• Language: English
• Subjects: AKT protein; Albumin; Analysis; Animals; Anticholesteremic Agents - pharmacology; Apoptosis; Atorvastatin; Atorvastatin - pharmacology; Biology and Life Sciences; Cardiovascular disease; Cell growth; Cholesterol; Chronic kidney failure; Creatinine; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetes Mellitus - prevention & control; Diabetic nephropathy; Down-Regulation - drug effects; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Glycogen Synthase Kinase 3 - metabolism; Hospitals; Hypertrophy; Immunoblotting; Immunohistochemistry; Injury prevention; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Kinases; Laboratory animals; Male; Medical schools; Medical treatment; Medicine and Health Sciences; Mice; Molecular chains; Molecular modelling; Mortality; NADPH Oxidase 4; NADPH Oxidases - metabolism; Nephropathy; Normalizing; NOX4 protein; Oxidative stress; Oxygen; Pharmacology; Phosphorylation; Phosphorylation - drug effects; Proliferating cell nuclear antigen; Protective Agents - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Renal cortex; Research and Analysis Methods; rho GTP-Binding Proteins - metabolism; rhoA GTP-Binding Protein; RhoA protein; Rodents; Signal Transduction - drug effects; Statins; Studies; Surface area; Type 2 diabetes; Up-Regulation - drug effects; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162731

Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *P