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Activation of protease-activated receptor (PAR) 1 by frog trefoil factor (TFF) 2 and PAR4 by human TFF2

Yong Zhang1, Guoyu Yu, Yanjie Wang

  • 1Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan, China.

Cellular and Molecular Life Sciences : CMLS
|April 5, 2011
PubMed

Insights

Human trefoil factor 2 (hTFF2) promotes epithelial cell migration and mucosal healing. This process is mediated by protease-activated receptor 4 (PAR4), highlighting a novel mechanism for tissue repair.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gastroenterology

Background:

  • Trefoil factors (TFFs) are crucial for epithelial repair after mucosal injury.
  • The specific receptors and molecular pathways for TFF-mediated epithelial cell migration remain largely unknown.
  • Previous studies indicated frog TFF2 activates protease-activated receptor (PAR) 1, suggesting a role for PARs in TFF function.

Purpose of the Study:

  • To investigate the role of protease-activated receptors (PARs) in human TFF2 (hTFF2)-induced epithelial cell migration and mucosal healing.
  • To identify the specific PAR involved in hTFF2-mediated epithelial responses.

Main Methods:

  • Utilized small interfering RNAs (siRNAs) to deplete specific PARs (PAR1, PAR2, PAR4) in epithelial cell lines.
  • Assessed epithelial cell migration in response to hTFF2 stimulation.
  • Measured ERK1/2 phosphorylation as an indicator of signaling pathway activation.
  • Expressed PAR4 in PAR4-negative cell lines to confirm its role.

Main Results:

  • hTFF2-stimulated epithelial cell migration was significantly inhibited by PAR4 depletion but not by PAR1 or PAR2 depletion.
  • PAR4-negative epithelial cell lines (AGS, LoVo) showed enhanced responsiveness to hTFF2 upon PAR4 expression, including increased ERK1/2 phosphorylation and migration.
  • These results strongly implicate PAR4 as the primary receptor mediating hTFF2's effects on epithelial cells.

Conclusions:

  • Human TFF2 promotes epithelial cell migration and contributes to mucosal healing through activation of PAR4.
  • This study elucidates a novel molecular mechanism involving TFF2 and PAR4 in epithelial repair processes.
  • Findings provide a foundation for further research into TFF and PAR functions in physiological and pathological contexts.

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