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

Author(s): Mengmeng Zhuang, Juan Le, Bo Zhu, Wenwen Zhang, Hao Yan, Pan Zhang, Ting Wang, Yong Sun*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 8 , 2020


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Abstract:

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Trefoil factor 3, JAK/STAT3 pathway, cell migration, cell adhesion, N-cadherin, E-cadherin.

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VOLUME: 17
ISSUE: 8
Year: 2020
Page: [993 - 1000]
Pages: 8
DOI: 10.2174/1570180817666200204104420
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