ADAMTS4, a disintegrin and metalloproteinase with thrombospondin motifs 4, is crucial in regulating the extracellular matrix (ECM), impacting its formation, homeostasis, and remodeling [3]. It is involved in multiple biological processes such as extracellular matrix remodeling, cell differentiation, and cytokine regulation [1,2,4].

In severe influenza virus infection, damage-responsive lung fibroblasts produce ADAMTS4, which, along with inflammatory cytokines, modifies the lung microenvironment, promoting immune cell infiltration at the expense of lung function, and its levels in the lower respiratory tract are associated with infection severity [1]. In the amnion at parturition, ADAMTS4 is a crucial proteolytic enzyme for versican cleavage, and its intra-amniotic injection in mice induces preterm birth [2]. In lung cancer, knockdown of ADAMTS4 inhibits cell proliferation, migration, and HUVECs tubule formation, while overexpression promotes these processes by stabilizing c-Myc and activating the MAPK signaling pathway [3]. Genetic ablation of Adamts4 in mice impedes NG2 proteolysis, leading to impaired oligodendrocyte differentiation and axonal myelination, and lessens myelin repair in adult brain tissue following demyelination [4]. In Alzheimer's disease, genetic knockout of ADAMTS4 in cultured cells and mouse plasma reduces the production of the amyloid biomarker APP669-711 [5]. In premature rupture of membranes, ADAMTS4 expression is increased and correlated with inflammasome activation in placenta and fetal membrane tissues of patients with PPROM and MPROM [6].

In conclusion, ADAMTS4 plays essential roles in various biological processes and diseases. Studies using gene knockout mouse models have revealed its functions in lung function during severe respiratory infections, parturition, lung cancer progression, oligodendrocyte differentiation and remyelination, Alzheimer's disease biomarker production, and premature rupture of membranes. These findings provide insights into potential therapeutic targets for related diseases.