Downregulation of MT2-MMP and MT5-MMP in ulcerative colitis serves a diagnostic predictor and potential therapeutic targets.

Abstract

Background: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by persistent inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) play a key role in extracellular matrix degradation, and their dysregulation is implicated in IBD. However, the specific role of membrane-type MMPs (MT-MMPs) in UC remains underexplored. This study investigates the expression of MT-MMPs in UC patients, including new cases and treatment-resistant patients, and evaluates their expression patterns compared to healthy people.

Methods and results: Colon biopsy samples were collected from three groups: healthy controls (n = 20), newly diagnosed UC patients (n = 20), and UC patients resistant to standard treatments (n = 20). The mRNA expression levels of MT-MMPs were assessed using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic utility of these MT-MMPs. Correlation analysis was also conducted to explore the relationship between MT-MMPs and inflammatory markers (CRP, ESR) and vitamin D levels. Out of 6 members of MT-MMPs, MT2-MMP, and MT5-MMP were significantly downregulated in new cases and resistant UC patients compared to controls (P < 0.0001). ROC analysis demonstrated high sensitivity and specificity for MT2-MMP and MT5-MMP in differentiating UC patients from healthy individuals. Additionally, MT2,5-MMP expression was negatively correlated with CRP, ESR, and vitamin D levels, indicating their possible modulation of systematic inflammation.

Conclusion: MT2-MMP and MT5-MMP are downregulated in UC and may serve as diagnostic biomarkers for disease severity. The findings highlight the need for further investigation into their therapeutic potential in modulating inflammation and tissue remodeling in UC.