Matrix Metalloproteinase-9 (MMP-9) in Psoriasis: Integrating Extracellular Matrix Remodeling, Neutrophil–Endothelial Crosstalk and Biomarker Evidence

Abstract

Psoriasis is a chronic immune-mediated inflammatory disease in which cytokine-driven epidermal activation is accompanied by extensive remodeling of the extracellular matrix, basement membrane, and cutaneous microvasculature. Matrix metalloproteinase-9 (MMP-9; gelatinase B) may provide an important link between these structural alterations and several key features of psoriatic inflammation, including neutrophil activation, endothelial dysfunction, vascular hyperpermeability, and leukocyte recruitment. This review critically examines the biological and clinical relevance of MMP-9 across the spectrum of psoriatic disease. Particular focus is given to the cellular sources and regulation of MMP-9, its expression in lesional and non-lesional skin, and its interactions with the IL-23/Th17, IL-17, TNF-α, IL-36, MAPK, and NF-κB signaling pathways. Experimental studies support a functional neutrophil–MMP-9–endothelium axis in which MMP-9 can promote endothelial activation, vasodilation, vascular hyperpermeability, and leukocyte transmigration. However, this mechanistic evidence derives predominantly from experimental systems, whereas human studies mainly demonstrate associations between psoriasis and increased tissue or circulating MMP-9. The interpretation of circulating MMP-9 is further complicated by sample type, enzymatic activation state, assay heterogeneity, treatment exposure, and inflammatory and cardiometabolic confounders. Overall, MMP-9 represents a biologically possible contributor to psoriatic tissue remodeling and vascular inflammation, but its causal importance in human psoriasis remains insufficiently established. Future studies should determine whether MMP-9 can contribute to validated phenotype-specific multimarker models. At present, its clinical utility as either a biomarker or therapeutic target remains exploratory.