scholarly journals Eribulin Does Not Prevent Epithelial-to-Mesenchymal Transition in HT-29 Intestinal Epithelial Cells

2017 ◽  
Vol 2 (4) ◽  
pp. 211-218
Author(s):  
Martin Leutenegger ◽  
Ramona Bruckner ◽  
Marianne R. Spalinger ◽  
Silvia Lang ◽  
Gerhard Rogler ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Ht 29

scholarly journals Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1104 ◽  
Author(s):  
Dolores Ortiz-Masiá ◽  
Laura Gisbert-Ferrándiz ◽  
Cristina Bauset ◽  
Sandra Coll ◽  
Céline Mamie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Wnt Signaling ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Fistula Tract ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Ht29 Cells

The pathogenesis of Crohn’s disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn’s disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis. EMT, as increased expression of Snail1, Snail2 and vimentin and reduction in E-cadherin, was analyzed in tissues and succinate-treated HT29 cells. The role played by SUCNR1 was studied by silencing its gene. Succinate levels and SUCNR1 expression are increased in B3-CD patients and correlate with EMT markers. SUCNR1 is detected in transitional cells lining the fistula tract and in surrounding mesenchymal cells. Grafts from wild type (WT) mice present increased succinate levels, SUCNR1 up-regulation and EMT activation, effects not observed in SUCNR1−/− tissues. SUCNR1 activation induces the expression of Wnt ligands, activates WNT signaling and induces a WNT-mediated EMT in HT29 cells. In conclusion, succinate and its receptor are up-regulated around CD-fistulas and activate Wnt signaling and EMT in intestinal epithelial cells. These results point to SUCNR1 as a novel pharmacological target for fistula prevention.

scholarly journals A KDM4-DBC1-SIRT1 Axis Contributes to TGF-b Induced Mesenchymal Transition of Intestinal Epithelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Baoyu Chen ◽  
Wenhui Dong ◽  
Tinghui Shao ◽  
Xiulian Miao ◽  
Yan Guo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Class Iii ◽  
Benzene Sulfonic Acid ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Lysine Deacetylase ◽  
Bowel Diseases

Intestinal fibrosis is one of the common pathophysiological processes in inflammatory bowel diseases (IBDs). Previously it has been demonstrated that epithelial-mesenchymal transition (EMT) can contribute to the development of intestinal fibrosis. Here we report that conditional ablation of SIRT1, a class III lysine deacetylase, in intestinal epithelial cells exacerbated 2, 4, 6-trinitro-benzene sulfonic acid (TNBS) induced intestinal fibrosis in mice. SIRT1 activity, but not SIRT1 expression, was down-regulated during EMT likely due to up-regulation of its inhibitor deleted in breast cancer 1 (DBC1). TGF-β augmented the recruitment of KDM4A, a histone H3K9 demethylase, to the DBC1 promoter in cultured intestinal epithelial cells (IEC-6) leading to DBC1 trans-activation. KDM4A depletion or inhibition abrogated DBC1 induction by TGF-β and normalized SIRT1 activity. In addition, KDM4A deficiency attenuated TGF-β induced EMT in IEC-6 cells. In conclusion, our data identify a KDM4-DBC1-SIRT1 pathway that regulates EMT to contribute to intestinal fibrosis.

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

2020 ◽  
Vol 17 (8) ◽  
pp. 993-1000
Author(s):  
Mengmeng Zhuang ◽  
Juan Le ◽  
Bo Zhu ◽  
Wenwen Zhang ◽  
Hao Yan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Intestinal Epithelial Cells ◽  
The Body ◽  
Intestinal Epithelial ◽  
Trefoil Factor ◽  
Stat3 Pathway ◽  
Ht 29 ◽  
E Cadherin

Objective: 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.

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