Related Experiment Video
Updated: Sep 9, 2025
07:23
Innervation of Human Intestinal Organoids
Published on: January 17, 2025
651
Microenvironmental TFPI2 in Hirschsprung Disease: Mechanisms in ENCC Development
Dong Sun1, Xintao Zhang2, Xue Ren2
1Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China; Department of Pediatric Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Journal of Pediatric Surgery
|September 1, 2025
Summary
Tissue factor pathway inhibitor 2 (TFPI2) is elevated in Hirschsprung disease (HSCR), inhibiting enteric neural crest cell (ENCC) function. This suggests TFPI2 is a potential therapeutic target for HSCR.
Area of Science:
- Developmental Biology
- Gastroenterology
- Molecular Biology
Background:
- Hirschsprung disease (HSCR) involves absent enteric ganglion cells due to defective enteric neural crest cell (ENCC) colonization.
- The intestinal microenvironment's role in HSCR pathogenesis is under investigation.
Purpose of the Study:
- To investigate the role of tissue factor pathway inhibitor 2 (TFPI2) in the intestinal microenvironment of HSCR.
- To elucidate the mechanisms by which TFPI2 affects ENCCs.
Main Methods:
- Analysis of transcriptomic datasets from HSCR patients and mouse models.
- Validation of TFPI2 expression using qRT-PCR, immunohistochemistry, and Western blotting.
- In vitro assessment of TFPI2 effects on ENCC proliferation, apoptosis, and migration, with pathway analysis and functional rescue experiments.
Main Results:
- TFPI2 expression is significantly elevated in HSCR aganglionic segments and fetal mouse intestines.
- TFPI2 inhibits ENCC proliferation and migration while promoting apoptosis.
- Downregulation of the PI3K-AKT signaling pathway is implicated, with partial rescue by IGF-1.
Conclusions:
- TFPI2 is identified as a novel microenvironmental factor contributing to ENCC dysfunction in HSCR.
- TFPI2 inhibits ENCCs by suppressing the PI3K-AKT signaling pathway.
- TFPI2 represents a potential therapeutic target for Hirschsprung disease.
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