TFF1 Promotes EMT-Like Changes through an Auto-Induction Mechanism

Autor: Antonello Petrella, Raffaella Belvedere, Valentina Bizzarro, Elena Romano, Alessandra Tosco, Roberta Esposito, Megi Vllahu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Epithelial-Mesenchymal Transition
Immunofluorescence
Response Elements
Catalysis
Article
Epigenesis
Genetic
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
Western blot
Stomach Neoplasms
Cell Line
Tumor
medicine
Humans
Epithelial–mesenchymal transition
Physical and Theoretical Chemistry
Promoter Regions
Genetic
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
TFF1
Regulation of gene expression
medicine.diagnostic_test
Mechanism (biology)
Chemistry
hypoxia
Organic Chemistry
epithelial to mesenchymal transition
General Medicine
Methylation
DNA Methylation
invasion
Hypoxia-Inducible Factor 1
alpha Subunit
In vitro
Cell Hypoxia
Computer Science Applications
Cell biology
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Gene Expression Regulation
Trefoil Factor-1
gene regulation
Function (biology)
Signal Transduction
Zdroj: International Journal of Molecular Sciences
Volume 19
Issue 7
International Journal of Molecular Sciences, Vol 19, Iss 7, p 2018 (2018)
Popis: Trefoil factor 1 (TFF1) is a small secreted protein expressed in the gastrointestinal tract where, together with the other two members of its family, it plays an essential role in mucosal protection and repair against injury. The molecular mechanisms involved in the protective function of all three TFF proteins are not fully elucidated. In this paper, we investigated the role of TFF1 in epithelial to mesenchymal transition (EMT) events. The effects of TFF1 on cellular models in normoxia and/or hypoxia were evaluated by western blot, immunofluorescence, qRT-PCR and trans-well invasion assays. Luciferase reporter assays were used to assess the existence of an auto-regulatory mechanism of TFF1. The methylation status of TFF1 promoter was measured by high-resolution melting (HRM) analysis. We demonstrate a TFF1 auto-induction mechanism with the identification of a specific responsive element located between &minus
583 and &minus
212 bp of its promoter. Our results suggest that TFF1 can regulate its own expression in normoxic, as well as in hypoxic, conditions acting synergistically with the hypoxia-inducible factor 1 (HIF-1&alpha
) pathway. Functionally, this auto-induction mechanism seems to promote cell invasion and EMT-like modifications in vitro. Additionally, exogenously added human recombinant TFF1 protein was sufficient to observe similar effects. Together, these findings suggest that the hypoxic conditions, which can be induced by gastric injury, promote TFF1 up-regulation, strengthened by an auto-induction mechanism, and that the trefoil peptide takes part in the epithelial-mesenchymal transition events eventually triggered to repair the damage.
Databáze: OpenAIRE
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