title: Effect of amlodipine on mouse renal interstitial fibrosis.
abstract: Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidney, but this change was inhibited by amlodipine (6.7mg/kg/day in drinking water). mRNA expression of heat shock protein (HSP) 47 and type IV collagen was increased in the kidneys of UUO mice. Amlodipine reduced the expression of both HSP47 and type IV collagen mRNAs. Phosphorylation of c-jun-N-terminal kinase (JNK) was significantly increased by UUO, but the change was inhibited by amlodipine. Collectively, these results suggest that amlodipine may inhibit the expression of HSP47 and type IV collagen by reducing phosphorylation of JNK and ameliorating the renal interstitial fibrosis induced by UUO.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan. Electronic address: shonma@takasaki-u.ac.jp.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Honma
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Mitazaki
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma 370-0033, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine
keywords: Amlodipine; Fibrosis; Heat shock protein 47; Type IV collagen; Unilateral ureteral obstruction; c-jun-N-terminal kinase (JNK)