The Role of Platelet-Activating Factor in Mesangial Pathophysiology

Platelet-activating factor (PAF) is a powerful proinflammatory mediator that displays an exceedingly diverse spectrum of biological effects. Importantly, PAF is shown to participate in a broad range of pathologic conditions. This review focuses on the role that PAF plays specifically in the pathophysiology of the kidney, the organ that is both a source and a target of PAF. Renal mesangial cells are responsible for glomerular PAF generation and, ultimately, are the victims of its excessive production. Mesangial pathology is widely acknowledged to reflect glomerular damage, which culminates in glomerulosclerosis and proteinuria. Therefore, modulation of mesangial cell responses would offer a pathophysiology-based therapeutic approach to prevent glomerular injury. However, the currently available therapeutic modalities do not allow for targeted intervention into these processes. A more profound understanding of the mechanisms that govern PAF metabolism and signaling in mesangial cells is important, because it could facilitate the quest for improved therapies for renal patients on the basis of PAF as a drug target.