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

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Trefoil factor 1 (TFF1) is crucial for gastrointestinal mucosal protection and repair.
• The precise molecular mechanisms underlying TFF1's protective functions remain incompletely understood.
• Epithelial-mesenchymal transition (EMT) is a key process in tissue repair.

Purpose of the Study:

• To investigate the role of TFF1 in epithelial-mesenchymal transition (EMT).
• To elucidate the regulatory mechanisms of TFF1 expression, especially under hypoxic conditions.
• To explore the functional consequences of TFF1 auto-induction in cellular models.

Main Methods:

• Western blot, immunofluorescence, and qRT-PCR to assess TFF1 effects.
• Trans-well invasion assays to evaluate cell motility.
• Luciferase reporter assays and HRM analysis to study TFF1 promoter regulation and methylation.

Main Results:

• A TFF1 auto-induction mechanism was identified, involving a promoter responsive element (-583 to -212 bp).
• TFF1 auto-regulation occurs in both normoxic and hypoxic conditions, synergizing with the HIF-1α pathway.
• TFF1 up-regulation and auto-induction promote in vitro cell invasion and EMT-like changes, effects mimicked by exogenous TFF1.

Conclusions:

• Hypoxia, often induced by gastric injury, up-regulates TFF1 via auto-induction.
• TFF1 plays a significant role in initiating epithelial-mesenchymal transition events during tissue repair.
• The TFF1 auto-induction pathway is a potential target for modulating gastrointestinal repair processes.