Rgn couples proliferative EGFR-JAK/STAT signaling and the notch/insulin differentiation-metabolism axis during epithelial repair in Drosophila - PubMed
6 hours ago
- #Regeneration
- #Signaling Pathways
- #DNA Damage
- Rgn deficiency in Drosophila intestinal stem cells disrupts Notch signaling, leading to a loss of ISCs and accumulation of enteroblasts (EBs).
- This disruption suppresses the insulin/TOR pathway, causing reactive oxygen species (ROS) accumulation and DNA double-strand breaks.
- The resulting CHK2/p53-dependent G2/M arrest and apoptosis cause progenitor loss and intestinal atrophy.
- Overexpression of S6K rescues ROS accumulation and proliferation defects, while constitutive EGFR or STAT92E activation restores ISC mitotic activity.
- Rgn acts as an integrator of Notch-driven differentiation, insulin-dependent redox control, and DNA damage surveillance.
- The study establishes Drosophila Rgn as a functional analog of human REG proteins, suggesting potential therapies for inflammatory bowel diseases.