| Authors: |
Elizabeth Smith3, Jennifer Baek1, Kimberly Curry1, and Rui Wang 1, 2
1Department of Surgery, Case Comprehensive Cancer Center, Case Western Reserve University 2Department of Surgery, University Hospitals Cleveland Medical Center 3Alabama College of Osteopathic Medicine |
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Abstract: |
Inflammatory bowel disease (IBD) is a group of inflammatory-driven diseases in the gastrointestinal (GI) tract that includes ulcerative colitis (UC) and Crohn’s disease (CD). IBD affects over 3 million people in the USA and puts patients at higher risk of developing colorectal cancer due to the chronic inflammation associated with IBD (data from Crohn’s & Colitis foundation, 2023). Treating the chronic inflammation remains a major challenge for treating patients with UC and lowering the risk of colorectal cancers. Several clinical studies have shown that elevated leucine rich ⍺2 glycoprotein 1 (LRG1) expression in the serum and inflamed colon mucosa of patients with IBD correlates with disease severity and the mechanism by which LRG1 promotes colonic inflammation in IBD is not fully understood1–3. Our preliminary data shows that: (1) Systemic LRG1 knockout attenuated disease severity in male mice with DSS-induced colitis as shown through disease symptoms and histopathology. (2) LRG1 may promote colonic inflammation by promoting neutrophil extracellular trap (NET) formation. Together, our data suggest that LRG1 plays a pro-inflammatory role in inflammatory bowel disease by promoting neutrophil mediated immunity and NET formation and suggest the potential of blocking LRG1 for patients with UC. Further investigations are needed to elucidate the mechanism by which LRG1 promotes NET formation. |