JAK/STAT3 Pathway in Human Intestinal Epithelial Cells During Trefoil Factor 3(TFF3) Mediated Cell Migration

JAK/STAT3 Pathway in Human Intestinal Epithelial Cells During Trefoil Factor 3(TFF3) Mediated Cell Migration
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三叶因子 3 (TFF3) 介导的细胞迁移过程中人肠上皮细胞中的 JAK/STAT3 通路

DOI:
10.2174/1570180817666200204104420
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发表时间:
2020-07
影响因子:
1
通讯作者:
Sun Yong
Sun Yong
中科院分区:
医学4区
文献类型:
--
作者:
Zhuang Mengmeng;Le Juan;Zhu Bo;Zhang Wenwen;Yan Hao;Zhang Pan;Wang Ting;Sun Yong

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三叶因子家族在身体的几种组织中表达,并提供胃和肠的保护和愈合。本研究以JAK抑制剂AG 490或60 μ g/ml人重组三叶因子预处理肠上皮细胞,Western Blotting检测磷酸化STAT 3、E-cadherin和N-cadherin的表达。通过定量真实的时间PCR评估基质金属蛋白酶、钙粘蛋白和N-钙粘蛋白的水平。通过transwell试验和划痕试验评估细胞迁移。免疫荧光法检测HT-29细胞中E-cadherin分子的减少。hTFF 3激活HT-29细胞中JAK/STAT 3通路。JAK/STAT 3通路机制对hTFF 3促进细胞迁移的影响。TFF 3促进细胞迁移与MMPs的基因转录增加相关。hTFF 3改变E-钙粘蛋白的表达。在HT-29细胞中,hTFF 3激活N-钙粘蛋白的表达,下调E-钙粘蛋白的表达。TFF 3可增加基质金属蛋白酶和N-钙粘蛋白的表达,降低E-钙粘蛋白的表达,而AG 490则相反。TFF 3促进细胞迁移,AG 490减缓迁移速率以控制水平。TFF 3激活JAK/STAT 3通路,该通路与肠上皮细胞迁移相关。
Trefoil factor family is expressed in several tissues of the body and provides gastric and intestinal protection and healing. This research aims to indicate the mechanism involved in its function.The intestinal epithelial cells were pretreated with JAK inhibitor AG490 or the concentration of 60ug/ml human recombinant trefoil factor, while the levels of phospho-STAT3, E-cadherin and N-cadherin were detected by Western Blotting. The levels of Matrix Metalloproteinases, Ecadherin and N-cadherin were evaluated by quantitative real time PCR. The cell migration was assessed by the transwell assay and the scratch assay. The immunofluorescence method was performed to detect the reduction of molecular E-cadherin.hTFF3 activates the JAK/STAT3 pathway in HT-29 cells. The effect of JAK/STAT3 pathway mechanism on cell migration promoted by hTFF3. TFF3 promoting cell migration is associated with increased gene transcription of MMPs. hTFF3 alters E-cadherin expression. hTFF3 activates the expression of N-cadherin and down-regulates E-cadherin expression in HT-29 Cells.We have shown that TFF3 activated the JAK/STAT3 pathway. TFF3 increased the level of Matrix Metalloproteinases and N-cadherin, decreased that of E-cadherin, while AG490 had the opposite effect. TFF3 accelerated cell migration and the AG490 relieved the migrating rate to control the levels. TFF3 activated JAK/STAT3 pathway which was associated with intestinal epithelial cell migration.
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