Endogenous Hyaluronan Promotes Intestinal Homeostasis and Protects against Murine Necrotizing Enterocolitis

Area of Science:

• Gastroenterology
• Developmental Biology
• Immunology

Background:

• Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants.
• Its development involves intestinal barrier dysfunction, microbial imbalance, and immune dysregulation.
• The role of endogenous hyaluronan (HA) in intestinal development and NEC pathogenesis is unclear.

Purpose of the Study:

• To investigate the function of endogenous hyaluronan (HA) in neonatal mouse intestinal development.
• To assess the impact of inhibiting HA signaling on NEC-like intestinal injury.

Main Methods:

• Neonatal mice were treated with PEP1, a peptide that inhibits HA receptor interactions, or a scrambled peptide control.
• Intestinal development was evaluated by measuring villi length, crypt depth, cell proliferation, and cell differentiation.
• Susceptibility to NEC-like injury and mortality rates were assessed in treated and control groups.

Main Results:

• PEP1 treatment significantly inhibited intestinal development, reducing villi length, crypt depth, and epithelial cell proliferation.
• Crypt fission activity was decreased in PEP1-treated mice.
• Mice treated with PEP1 exhibited increased susceptibility to NEC-like injuries, higher mortality, and more severe histological damage.

Conclusions:

• Endogenous hyaluronan plays a vital role in supporting normal intestinal development.
• Inhibition of HA signaling compromises intestinal integrity and increases susceptibility to NEC-like injury.
• Targeting HA interactions may offer a therapeutic strategy for preventing or treating NEC.