Tempol Attenuates Renal Fibrosis in Mice with Unilateral Ureteral Obstruction: The Role of PI3K-Akt-FoxO3a Signaling.
10.3346/jkms.2014.29.2.230
- Author:
Hye Eun YOON
1
;
Soo Jeong KIM
;
Sung Jun KIM
;
Sungjin CHUNG
;
Seok Joon SHIN
Author Information
1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. imkidney@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
FoxO3a Protein, Mouse;
Oxidative Stress;
Apoptosis;
Renal Fibrosis;
Unilateral Ureteral Obstruction
- MeSH:
Animals;
Antioxidants/pharmacology/therapeutic use;
Collagen/metabolism;
Cyclic N-Oxides/*pharmacology/therapeutic use;
Fibrosis;
Forkhead Transcription Factors/*metabolism;
Hydrogen Peroxide/metabolism;
Kidney Diseases/drug therapy/metabolism/pathology;
Lipid Peroxidation;
Male;
Mice;
Mice, Inbred C57BL;
Oxidative Stress/drug effects;
Phosphatidylinositol 3-Kinases/*metabolism;
Phosphorylation/drug effects;
Proto-Oncogene Proteins c-akt/*metabolism;
Severity of Illness Index;
Signal Transduction/*drug effects;
Spin Labels;
Superoxide Dismutase/metabolism;
Ureteral Obstruction/complications/drug therapy/*metabolism/pathology
- From:Journal of Korean Medical Science
2014;29(2):230-237
- CountryRepublic of Korea
- Language:English
-
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, alpha-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-beta1 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.
