title: Tempol attenuates renal fibrosis in mice with unilateral ureteral obstruction: the role of PI3K-Akt-FoxO3a signaling.
abstract: This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, α-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-β1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. ; Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Hye Eun
authors.identifier: 0000-0002-6347-7282
authors.initials: HE
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. ; Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. ; Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Seok Joon
authors.identifier: 0000-0001-7642-2849
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D005355:Fibrosis; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D013113:Spin Labels; D003094:Collagen; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C001803:tempol
keywords: Apoptosis; FoxO3a Protein, Mouse; Oxidative Stress; Renal Fibrosis; Unilateral Ureteral Obstruction