The Roles of sPLA₂s in Skin Homeostasis and Disease

Among the phospholipase A(2) (PLA(2)) family, the secreted PLA(2) (sPLA(2)) family in mammals contains 11 members that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using knockout and/or transgenic mice for a nearly full set of sPLA(2)s, in combination with comprehensive lipidomics, have revealed the diverse pathophysiological roles of sPLA(2)s in various biological events. Individual sPLA(2)s exert specific functions within tissue microenvironments, likely through the hydrolysis of extracellular phospholipids. Lipids are an essential biological component for skin homeostasis, and disturbance of lipid metabolism by deletion or overexpression of lipid-metabolizing enzymes or lipid-sensing receptors often leads to skin abnormalities that are easily visible on the outside. Over the past decades, our studies using knockout and transgenic mice for various sPLA(2)s have uncovered several new aspects of these enzymes as modulators of skin homeostasis and disease. This article summarizes the roles of several sPLA(2)s in skin pathophysiology, providing additional insight into the research fields of sPLA(2)s, lipids, and skin biology.