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题名: Assessment of cadmium-induced nephrotoxicity using a kidney-on-a-chip device
作者: Li, Zhongyu1, 2;  Jiang, Lei1;  Tao, Tingting1;  Su, Wentao1;  Guo, Yaqiong1, 2;  Yu, Hao1;  Qin, Jianhua1, 2
刊名: TOXICOLOGY RESEARCH
发表日期: 2017-05-01
DOI: 10.1039/c6tx00417b
卷: 6, 页:372-380
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Toxicology
研究领域[WOS]: Toxicology
英文摘要: Cadmium (Cd) is a common environmental pollutant. Its effects on human health have attracted great attention. The kidney is the organ that is the most affected by Cd exposure. Thus, it is highly desirable to develop a reliable model to evaluate Cd-induced nephrotoxicity in vitro. We present a kidney-on-a-chip with three compartmentalized culture chambers to examine Cd-induced nephrotoxicity. The culture and collection channels represent the capillary and the glomerular capsule sides of the glomerular filtration barrier, respectively. Isolated primary rat glomerular endothelial cells (GECs) were cultured on the side surface of the middle gel channel. The integrated GEC layer demonstrated the selective permeability of the renal barrier. Therefore, it was further utilized to study the nephrotoxicity induced by Cd exposure at different concentrations. Cd induced significant cytotoxicity and disrupted the expression of tight junction protein ZO-1 in a dose-dependent manner. Moreover, Cd exposure increased the permeability of the endothelial layer to large molecules, immunoglobulin G and albumin. These results facilitate the understanding of the underlying mechanism of kidney dysfunction and glomerular disease. This is the first study on Cd-induced nephrotoxicity using primary GECs in a microfluidic device. The kidney-on-a-chip device enables direct visualization and quantitative analysis of GEC responses to Cd in real time. It may provide a micro-scale platform based on the human system for nephrotoxicity testing under varying environmental exposure.
关键词[WOS]: DRUG-INDUCED NEPHROTOXICITY ;  OXIDATIVE STRESS ;  CELL-CULTURE ;  IN-VITRO ;  TOXICITY ;  APOPTOSIS ;  EXPOSURE ;  PATHWAY ;  LIVER ;  ACTIVATION
语种: 英语
WOS记录号: WOS:000401000400012
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/152300
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

Recommended Citation:
Li, Zhongyu,Jiang, Lei,Tao, Tingting,et al. Assessment of cadmium-induced nephrotoxicity using a kidney-on-a-chip device[J]. TOXICOLOGY RESEARCH,2017,6:372-380.
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