title: Nanosized titanium dioxide resulted in the activation of TGF-β/Smads/p38MAPK pathway in renal inflammation and fibration of mice.
abstract: Titanium dioxide nanoparticles (TiO2 NPs) have been demonstrated to damage the kidneys. However, whether chronic nephritis leads to renal fibration or the fibrosis is associated with the activation of TGF-β/Smads/p38MAPK pathway caused by TiO2 NPs exposure is not well understood. Forty male mice were separately exposed to 0, 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 6 months. Renal biochemical functions and levels of TGF-β/Smads/p38MAPK pathway-related markers and extracellular matrix (ECM) expression in the kidneys were investigated. The findings showed that subchronic TiO2 NPs exposure increased levels of urinary creatisix (Cr), N-acetyl-glucosaminidase, and vanin-1, resulted in severe renal inflammation and fibration. Furthermore, TiO2 NP exposure upregulated expression of transforming growth factor-β1 (TGF-β1, 0.07- to 2.72-fold), Smad2 (0.42- to 1.63-fold), Smad3 (0.02- to 1.94-fold), ECM (0.15- to 2.75-fold), α-smooth muscle actin (0.14- to 3.06-fold), p38 mitogen-activated protein kinase (p38MAPK, 0.11- to 3.78-fold), and nuclear factor-κB (0.4- to 2.27-fold), and downregulated Smad7 (0.05- to 0.61-fold) expression in mouse kidney. Subchronic TiO2 NPs exposure induced changes of renal characteristics towards inflammation and fibration may be mediated via TGF-β/Smads/p38MAPK pathway, and the uses of TiO2 NPs should be carried out cautiously, especially in humans. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1452-1461, 2016.
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: F
authors: F
authors: Hong
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: N
authors: N
authors: Wu
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: Y
authors: Y
authors: Ge
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: Y
authors: Y
authors: Zhou
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: T
authors: T
authors: Shen
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: Q
authors: Q
authors: Qiang
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: Q
authors: Q
authors: Zhang
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: M
authors: M
authors: Chen
authors: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.|School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.
authors: Y
authors: Y
authors: Wang
authors: Library of Soochow University, Suzhou, 215123, China.
authors: L
authors: L
authors: Wang
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: J
authors: J
authors: Hong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004327:Drinking Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology* / Q000652:urine; D007668:Kidney / Q000473:pathology*; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D014025:Titanium / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C009495:titanium dioxide; D014025:Titanium; D048051:p38 Mitogen-Activated Protein Kinases
keywords: TGF-β/Smads/p38MAPK pathway; mice; renal fibration; renal inflammation; titanium dioxide nanoparticles