Regulation of Epithelial-to-Mesenchymal Transition Using Biomimetic Fibrous Scaffolds.
Regulation of Epithelial-to-Mesenchymal Transition Using Biomimetic Fibrous Scaffolds.
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DOI：
10.1021/acsami.6b05646
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发表时间：
2016-07-20
影响因子：
9.5
通讯作者：
Jia, Xinqiao
中科院分区：
文献类型：
--
作者：
Ravikrishnan, Anitha;Ozdemir, Tuba;Bah, Mohamed;Baskerville, Karen A.;Shah, S. Ismat;Rajasekaran, Ayyappan K.;Jia, Xinqiao
关键词：
上皮-间充质转化（EMT）是一个在胚胎发生、癌变和组织纤维化过程中发生的生物学过程。在EMT期间，具有立方结构的极化上皮细胞采用细长的成纤维细胞样形态。这个过程伴随着许多EMT特异性分子标记的表达。虽然导致EMT的分子机制已经很好地建立，但基质形貌和微观结构的影响尚未清楚地阐明。通过聚己内酯（PCL）的静电纺丝制备了模拟基底膜的网状结构的合成支架，其平均纤维直径为0.5 μm和5 μm，并用于测试纤维直径对EMT的意义。将细胞粘附肽基序缀合至纤维表面以促进细胞附着。在这些基质上生长的Madin-Darby犬肾（MDCK）细胞显示出不同的表型。在0.5 μm基质上，细胞生长为具有上皮表型的致密集落。在5 μm的支架上，细胞更加分散，看起来更像成纤维细胞。加入EMT诱导剂肝细胞生长因子（HGF）后，在0.5 μm支架上生长的细胞发生明显的分散，表现为细胞形态改变、粘着斑复合物定位、细胞-细胞粘附减弱和间充质标志物上调。相比之下，HGF没有诱导在5.0 μm支架上培养的MDCK细胞的明显分散。总的来说，我们的研究结果表明，基底膜中发现的蛋白质纤维直径的改变可能会对上皮组织和散射产生足够的干扰，这可能对疾病的进展产生重要影响。
Epithelial-to-mesenchymal transition (EMT) is a well-studied biological process that takes place during embryogenesis, carcinogenesis and tissue fibrosis. During EMT, the polarized epithelial cells with a cuboidal architecture adopt an elongated fibroblast-like morphology. This process is accompanied by the expression of many EMT-specific molecular markers. While the molecular mechanism leading to EMT has been well established, the effects of matrix topography and microstructure have not been clearly elucidated. Synthetic scaffolds mimicking the mesh-like structure of the basement membrane with an average fiber diameter of 0.5 μm and 5 μm were produced via electrospinning of poly(ε-caprolactone) (PCL) and were used to test the significance of fiber diameter on EMT. Cell-adhesive peptide motifs were conjugated to the fiber surface to facilitate cell attachment. Madin-Darby Canine Kidney (MDCK) cells grown on these substrates showed distinct phenotypes. On 0.5 μm substrates, cells grew as compact colonies with an epithelial phenotype. On 5 μm scaffolds, cells were more individually dispersed and appeared more fibroblastic. Upon addition of hepatocyte growth factor (HGF), an EMT inducer, cells grown on the 0.5 μm scaffold underwent pronounced scattering, as evidenced by the alteration of cell morphology, localization of focal adhesion complex, weakening of cell-cell adhesion, and upregulation of mesenchymal markers. By contrast, HGF did not induce a pronounced scattering of MDCK cells cultured on the 5.0 μm scaffold. Collectively, our results show that the alteration of the fiber diameter of proteins found in the basement membrane may create enough disturbances in epithelial organization and scattering that might have important implications in disease progression.
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影响因子：
3.9
作者：
Causa, Filippo;Battista, Edmond;Netti, Paolo A.
通讯作者：
Netti, Paolo A.
影响因子：
7.8
作者：
de Rooij, J;Kerstens, A;Waterman-Storer, CM
通讯作者：
Waterman-Storer, CM
影响因子：
5.5
作者：
Grieshaber, Sarah E.;Farran, Alexandra J. E.;Lin-Gibson, Sheng;Kiick, Kristi L.;Jia, Xinqiao
通讯作者：
Jia, Xinqiao
影响因子：
4.6
作者：
Eldsäter, C;Erlandsson, B;Karlsson, S
通讯作者：
Karlsson, S
DOI：
10.1088/1748-6041/10/1/015018
发表时间：
2015-01-29
期刊：
Biomedical materials (Bristol, England)
影响因子：
--
作者：
Bean AC;Tuan RS
通讯作者：
Tuan RS