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 |
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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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