title: Pitavastatin suppresses hyperglycaemia-induced podocyte injury via bone morphogenetic protein-7 preservation.
abstract: Podocytes form the essential components of the glomerular filtration barrier and play a critical role in diabetic nephropathy. Recent evidence suggests that HMG-CoA reductase inhibitors (statins) exert renoprotective effects. We investigated whether pitavastatin directly suppresses hyperglycaemia-induced podocyte injury using cultured podocytes and, if so, the mechanism of the beneficial effects. Cultured podocytes were exposed to media containing normal (NG; 5 mmol/L) or high (HG; 25 mmol/L) glucose for 1 week. HG increased the lethal injury of podocytes and disruption of F-actin fibers, and reduced the mRNA expression of novel podocyte markers, synaptopodin and Wilms tumor-1 (WT-1), in association with decreased bone morphogenetic protein-7 (BMP-7) expression. Pitavastatin (100 nmol/L) reduced podocyte injury and restored the mRNA expression of synaptopodin and WT1; however, these protective effects were abolished by BMP-7 siRNA. Additionally, pitavastatin suppressed HG-induced Rho kinase activation, as assessed by the phosphorylation level of myosin phosphatase targeting subunit 1 (MYTP1), and C3 exotoxin, a Rho inhibitor, mimicked the effect of pitavastatin on BMP-7 preservation. Pitavastatin attenuates hyperglycaemia-induced podocyte injury via Rho-Rho kinase-dependent BMP-7 preservation.
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohigashi
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobara
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toba
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isezaki, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D005947:Glucose; C108475:pitavastatin
keywords: BMP-7; diabetic nephropathy; podocyte; statin