Inhibition of Matriptase Activity Results in Decreased Intestinal Epithelial Monolayer Integrity In Vitro.

Area of Science:

• Gastroenterology
• Cell Biology
• Biochemistry

Background:

• Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBD).
• Matriptase, a cell surface protease, is implicated in regulating epithelial functions.
• Understanding matriptase's role is crucial for IBD pathogenesis and therapeutic strategies.

Purpose of the Study:

• To investigate the role of matriptase in maintaining intestinal barrier integrity.
• To characterize the effects of matriptase inhibition on epithelial cell function using a specific inhibitor.

Main Methods:

• Utilized porcine IPEC-J2 cell monolayers as an in vitro small intestinal model.
• Administered MI-432, a matriptase inhibitor, and assessed its effects on barrier function.
• Measured transepithelial electrical resistance (TER) and analyzed oxidative species distribution and protein localization.

Main Results:

• Matriptase inhibition by MI-432 significantly decreased TER, indicating barrier dysfunction.
• Short-term inhibition altered oxidative species distribution, with partial compensation upon prolonged treatment.
• Changes in matriptase staining and occludin localization suggested modulation of tight junctions.

Conclusions:

• Matriptase is essential for maintaining intestinal barrier integrity.
• Inhibition of matriptase can lead to paracellular gate opening and barrier disruption.
• Matriptase dysfunction may contribute to the 'leaky gut syndrome' in IBD.