Induction of epithelial-to-mesenchymal transition in proximal tubular epithelial cells on microfluidic devices.
Induction of epithelial-to-mesenchymal transition in proximal tubular epithelial cells on microfluidic devices.
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微流体装置上近端肾小管上皮细胞上皮-间质转化的诱导。
DOI：
10.1016/j.biomaterials.2013.10.070
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发表时间：
2014-02
期刊：
影响因子：
14
通讯作者：
Qin, Jianhua
中科院分区：
文献类型：
--
作者：
Zhou, Mengying;Ma, Huipeng;Lin, Hongli;Qin, Jianhua
在蛋白尿肾病中，上皮细胞向间质细胞转化（EMT）是导致肾间质纤维化的重要机制。EMT在纤维化发病机制中的确切作用仍然存在争议，部分原因是缺乏合适的体外模型。我们开发了两种微流控和隔室芯片，再现了近端肾小管上皮细胞在体内的流体和三维微环境。使用一个微流体装置，我们用健康人血清、热灭活血清和补体C3a的流动刺激上皮细胞，这模拟了近端小管内的尿液流动。我们观察到暴露于血清蛋白的上皮细胞发生凋亡或发展为间充质表型。将细胞与C3 a一起孵育也诱导了类似的特征。然而，暴露于热灭活血清的细胞没有采用间充质表型。此外，我们成功地记录了细胞形态学的变化和过程中的迁移到基底膜提取液EMT实时使用另一个三维微型设备。总之，我们已经建立了一个细胞培养系统，在一定程度上模仿的天然微环境的近端小管。我们的数据表明，EMT确实发生在暴露于血清蛋白的上皮细胞中，而C3 a在这一病理过程中发挥着至关重要的作用。
In proteinuric nephropathy, epithelial-to-mesenchymal transition (EMT) is an important mechanism that causes renal interstitial fibrosis. The precise role of EMT in the pathogenesis of fibrosis remains controversial, partly due to the absence of suitablein vitroorin vivomodels. We developed two microfluidic and compartmental chips that reproduced the fluidic and three-dimensional microenvironment of proximal tubular epithelial cellsin vivo. Using one microfluidic device, we stimulated epithelial cells with a flow of healthy human serum, heat-inactivated serum and complement C3a, which mimicked the flow of urine within the proximal tubule. We observed that epithelial cells exposed to serum proteins became apoptotic or developed a mesenchymal phenotype. Incubating cells with C3a induced similar features. However, cells exposed to heat-inactivated serum did not adopt the mesenchymal phenotype. Furthermore, we successfully recorded the cellular morphological changes and the process of transmigration into basement membrane extract during EMT in real-time using another three-dimensional microdevice. In conclusion, we have established a cell-culture system that mimics the native microenvironment of the proximal tubule to a certain extent. Our data indicates that EMT did occur in epithelial cells that were exposed to serum proteins, and C3a plays an essential role in this pathological process.
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影响因子：
3
作者：
Grgic, Ivica;Duffield, Jeremy S.;Humphreys, Benjamin D.
通讯作者：
Humphreys, Benjamin D.
影响因子：
13.6
作者：
Tang, Ziyong;Lu, Bao;Sheerin, Neil S.
通讯作者：
Sheerin, Neil S.
使用集成微流体装置进行基于细胞的高内涵筛选
影响因子：
6.1
作者：
Ye, Nannan;Qin, Jianhua;Lin, Bingcheng
通讯作者：
Lin, Bingcheng
影响因子：
32.5
作者：
R. Koesters;B. Kaissling;M. Lehir;N. Picard;F. Theilig;R. Gebhardt;A. Glick;Brunhilde Hähnel;
通讯作者：
R. Koesters;B. Kaissling;M. Lehir;N. Picard;F. Theilig;R. Gebhardt;A. Glick;Brunhilde Hähnel;
DOI：
10.1152/ajprenal.00426.2010
发表时间：
2011-04-01
影响因子：
4.2
作者：
Lin, Hongli;Wang, Dapeng;Shan, Lujuan
通讯作者：
Shan, Lujuan