Volume 104, Issue 6 pp. 1452-1461
Original Article

Nanosized titanium dioxide resulted in the activation of TGF-β/Smads/p38MAPK pathway in renal inflammation and fibration of mice

F Hong

Corresponding Author

F Hong

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

These authors contributed equally to this work.

Correspondence to: F. Hong; e-mail: [email protected]Search for more papers by this author
N Wu

N Wu

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

These authors contributed equally to this work.

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Y Ge

Y Ge

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

These authors contributed equally to this work.

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Y Zhou

Y Zhou

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

These authors contributed equally to this work.

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T Shen

T Shen

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

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Q Qiang

Q Qiang

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

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Q Zhang

Q Zhang

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

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M Chen

M Chen

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

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Y Wang

Y Wang

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

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L Wang

L Wang

Library of Soochow University, Suzhou, 215123 China

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J Hong

J Hong

Medical College of Soochow University, Suzhou, 215123 China

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First published: 06 February 2016
Citations: 30

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.

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