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Tempol attenuates renal fibrosis in mice with unilateral ureteral obstruction: the role of PI3K-Akt-FoxO3a signaling
- Source :
- Journal of Korean Medical Science
- Publication Year :
- 2013
-
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. Graphical Abstract
- Subjects :
- Male
Apoptosis
medicine.disease_cause
urologic and male genital diseases
Severity of Illness Index
Antioxidants
Lipid peroxidation
chemistry.chemical_compound
Mice
Phosphatidylinositol 3-Kinases
Fibrosis
Phosphorylation
Forkhead Box Protein O3
Forkhead Transcription Factors
General Medicine
Nephrology
Kidney Diseases
Original Article
Collagen
Signal Transduction
Ureteral Obstruction
medicine.medical_specialty
Unilateral Ureteral Obstruction
Biology
Renal Fibrosis
Superoxide dismutase
Cyclic N-Oxides
Internal medicine
medicine
Renal fibrosis
Animals
Protein kinase B
PI3K/AKT/mTOR pathway
urogenital system
Superoxide Dismutase
Hydrogen Peroxide
medicine.disease
Mice, Inbred C57BL
Oxidative Stress
Endocrinology
chemistry
Immunology
Tubulointerstitial fibrosis
biology.protein
Spin Labels
Lipid Peroxidation
FoxO3a Protein, Mouse
Proto-Oncogene Proteins c-akt
Oxidative stress
Subjects
Details
- ISSN :
- 15986357
- Volume :
- 29
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Korean medical science
- Accession number :
- edsair.doi.dedup.....3d5ea6279b8325766f111be2381f9b96