Hong F, Wu N, Ge Y, Zhou Y, Shen T, Qiang Q, Zhang Q, Chen M, Wang Y, Wang L, Hong J
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.
J Biomed Mater Res A. 2016 Jun;104(6):1452-61. doi: 10.1002/jbm.a.35678. Epub 2016 Feb 21.
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.
二氧化钛纳米颗粒（TiO2 NPs）已被证明会损害肾脏。然而，慢性肾炎是否会导致肾纤维化，或者这种纤维化是否与TiO2 NPs暴露引起的TGF-β/Smads/p38MAPK信号通路激活有关，目前尚不清楚。将40只雄性小鼠分别暴露于0、2.5、5或10 mg/kg体重的TiO2 NPs中，持续6个月。研究了肾脏的生化功能、TGF-β/Smads/p38MAPK信号通路相关标志物的水平以及肾脏中细胞外基质（ECM）的表达。结果表明，亚慢性TiO2 NPs暴露会增加尿肌酐（Cr）、N-乙酰氨基葡萄糖苷酶和血管生成素-1的水平，导致严重的肾脏炎症和纤维化。此外，TiO2 NPs暴露上调了小鼠肾脏中转化生长因子-β1（TGF-β1，0.07至2.72倍）、Smad2（0.42至1.63倍）、Smad3（0.02至1.94倍）、ECM（0.15至2.75倍）、α-平滑肌肌动蛋白（0.14至3.06倍）、p38丝裂原活化蛋白激酶（p38MAPK，0.11至3.78倍）和核因子-κB（0.4至2.27倍）的表达，并下调了Smad7（0.05至0.61倍）的表达。亚慢性TiO2 NPs暴露诱导的肾脏向炎症和纤维化特征的变化可能是通过TGF-β/Smads/p38MAPK信号通路介导的，TiO2 NPs的使用应谨慎进行，尤其是在人体中。© 2016 Wiley Periodicals, Inc.《生物医学材料研究杂志A部分》：104A：1452 - 1461，2016年。
