The differential roles of Giardia duodenalis-secreted tenascins in inducing intestinal epithelial cell apoptosis and the attributed EGFR-STAT3 axis regulation

Intestinal epithelial cell (IEC) apoptosis is a critical component of giardiasis development, yet the underlying mechanisms have remained poorly understood. This study investigates the role of Giardia duodenalis-secreted tenascins (GdTNCs) in this process. The research demonstrates that GdTNC-1 and GdTNC-2 are actively secreted by trophozoites and play differential roles in inducing apoptosis. Specifically, GdTNC-1 was found to interact with the Epidermal Growth Factor Receptor (EGFR), leading to the suppression of the STAT3 signaling pathway, which normally protects cells from death. By inhibiting this survival axis, the parasite facilitates the breakdown of the intestinal barrier. These findings clarify the pathogenic strategy of Giardia and highlight the EGFR-STAT3 axis as a potential focus for future drug development to mitigate the impact of diarrheal diseases caused by this parasite.