Neutrophilic HGF-MET Signalling Exacerbates Intestinal Inflammation

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Ulcerative colitis (UC) involves neutrophil infiltration and tissue damage, but the precise mechanisms are unclear.
• Hepatocyte growth factor (HGF) and its receptor c-MET (MET) are crucial for neutrophil function.
• The role of HGF-MET signaling specifically within neutrophils in UC pathogenesis requires elucidation.

Purpose of the Study:

• To investigate the function of HGF-MET signaling in neutrophils from UC patients.
• To determine the role of HGF-MET signaling in neutrophils during experimental intestinal inflammation in mice.

Main Methods:

• Assessed HGF levels in serum and colonic biopsies from healthy controls and UC patients.
• Utilized dextran sodium sulfate (DSS) colitis model in wild-type and neutrophil-specific MET-deficient mice.
• Analyzed immune cell infiltration, disease severity, and cytokine production.

Main Results:

• Elevated HGF in active UC patients and during DSS colitis.
• Increased MET expression on neutrophils in inflamed colons.
• Neutrophil-specific MET deficiency ameliorated DSS colitis severity and reduced TH17 cell numbers.

Conclusions:

• Neutrophilic HGF-MET signaling significantly contributes to intestinal inflammation and damage in UC.
• Targeting the HGF-MET pathway in neutrophils presents a potential novel therapeutic avenue for UC.