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Nanosized titanium dioxide resulted in the activation of TGF ‐β/ S mads/p38 MAPK pathway in renal inflammation and fibration of mice
Author(s) -
Hong F,
Wu N,
Ge Y,
Zhou Y,
Shen T,
Qiang Q,
Zhang Q,
Chen M,
Wang Y,
Wang L,
Hong J
Publication year - 2016
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35678
Subject(s) - inflammation , transforming growth factor , extracellular matrix , kidney , p38 mitogen activated protein kinases , fibrosis , signal transduction , microbiology and biotechnology , mapk/erk pathway , medicine , endocrinology , materials science , chemistry , biology
Titanium dioxide nanoparticles (TiO 2 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 TiO 2 NPs exposure is not well understood. Forty male mice were separately exposed to 0, 2.5, 5, or 10 mg/kg body weight TiO 2 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 TiO 2 NPs exposure increased levels of urinary creatisix (Cr), N ‐acetyl‐glucosaminidase, and vanin‐1, resulted in severe renal inflammation and fibration. Furthermore, TiO 2 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 TiO 2 NPs exposure induced changes of renal characteristics towards inflammation and fibration may be mediated via TGF‐β/Smads/p38MAPK pathway, and the uses of TiO 2 NPs should be carried out cautiously, especially in humans. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1452–1461, 2016.