Inflammatory indices reflect distinct pathogenic cellular programs driving sepsis progression: The role of mmp9...

Sepsis is a severe systemic inflammatory response syndrome in which matrix metalloproteinase 9 (MMP9) plays a key role in inflammatory response and cell migration. In this study, we analyzed different sepsis phenotypes to explore the role of MMP9 in promoting the progression of sepsis, especially how it affects the inflammatory index and related pathogenic cell programs. A standardized cecal ligation puncture (CLP) model was used to evaluate the inflammatory response in sepsis. The experiments followed animal ethical principles and extracted proteins and performed SDS-PAGE analysis for mass spectrometry identification. The samples were separated using filter-assisted sample preparation (FASP) and peptide digestion techniques, and the peptides were separated by ultra-high performance liquid chromatography (UHPLC). Subsequently, proteomic analysis, RNA extraction and differential expression analysis were performed on the data, and bioinformatics and machine learning methods were combined to evaluate the inflammatory index of both in vivo and in vitro samples. Through the integration of admission parameters, different sepsis endotypes and their clinical phenotypes were identified. Significantly, elevated MMP9 expression was found to be strongly associated with inflammatory indices such as NLR and PLR in patients with sepsis, suggesting that MMP9 may be involved in the proliferation of immune cells and the activation of their pro-inflammatory and hypoxic programs. Experimental CLP models validate the pathogenic cellular programs associated with NLR and PLR, demonstrating the critical role of MMP9 in the dynamic progression of sepsis.