Tetraspanin-Mediated ADAM10 Regulation in Sepsis and Potential Therapeutic Implications

Abstract

Excessive inflammatory responses in sepsis result in multiorgan dysfunction, with the majority of these responses being modulated by the activity of a disintegrin and metalloproteinase 10 (ADAM10). Due to the widespread distribution of ADAM10 and its numerous substrates, therapies targeting ADAM10 will have a range of physiological effects, including modulating inflammation, but may also cause toxic side effects. Precise therapeutic targets for regulating ADAM10 in specific diseases are needed. In several studies, tetraspanin family members have been identified as regulators of specific proteins, including ADAM10. In various cell types, the identical tetraspanin exhibits distinct effects on the regulation of ADAM10, indicating that tetraspanins possess cell-specific roles in modulating ADAM10. Furthermore, the interaction of diverse tetraspanins with ADAM10 results in the cleavage of various substrates. In this review, we provide a summary of the diverse tetraspanins that are currently recognized to interact with ADAM10 to identify potential new targets for regulating ADAM10 in sepsis.

Keywords: ADAM10 protein; inflammation; sepsis; tetraspanins.