title: Role of cyclooxygenase-2 in the development of interstitial fibrosis in kidneys following unilateral ureteral obstruction in mice.
abstract: Unilateral ureteral obstruction (UUO) induced tubulointerstitial fibrosis in kidneys mimics the pathogenesis of chronic kidney diseases and is considered a suitable model for studying the mechanisms leading to fibrosis. To study the role of cyclooxygenase-2 (COX-2) in kidney fibrosis, we investigated whether a selective COX-2 inhibitor, celecoxib, affected renal interstitial fibrosis during UUO in mice. To induce UUO, the left proximal ureter was ligated in male C57BL/6 mice. The mice were fed a diet with or without celecoxib from the day of UUO induction. Following UUO, the renal pelvis was observed to be dilated and the kidney cortex was significantly thinner than that of sham-operated mice. Immunofluorescent staining of type I, III, and IV collagen in UUO kidneys revealed that interstitial collagen deposition was significantly increased in the celecoxib-treated group. Expression of type I, III, and IV collagen in UUO kidneys was also significantly higher in the celecoxib-treated group than in the vehicle-treated group. In the celecoxib-treated group, mRNA levels of TGF-β/FGF-2 were also significantly higher than those in the vehicle-treated group. The present study demonstrates that COX-2 plays a protective role against fibrosis in UUO kidneys and suggests that supplementation of COX-2 products, such as PG analogues, will be a good option for preventing interstitial fibrosis.
authors.affiliation: Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan; Nephrology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kamata
authors.affiliation: Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hosono
authors.affiliation: Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Nephrology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: Kouju
authors.initials: K
authors.lastname: Kamata
authors.affiliation: Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0374, Japan. Electronic address: mmajima@med.kitasato-u.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Majima
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D045604:Extracellular Fluid / Q000187:drug effects / Q000201:enzymology; D005355:Fibrosis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2
keywords: COX-2; FGF; Fibrosis; Kidney; TGF; Unilateral ureteral obstruction