Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells

Lysophosphatidic acid (LPA) is the smallest and structurally simplest of all glycerophospholipids. LPA is a normal constituent of serum and binds with high affinity to albumin while retaining its biological activity. The effects of LPA are pleiotropic and range from mitogenesis to stress fiber formation. In this report, we demonstrate two novel functions for LPA. LPA acts as a survival factor to inhibit apoptosis of primary cultures of mouse renal proximal tubular (MPT) cells. LPA also acts as a potent mitogen for MPT cells. The ability of LPA to act as both a survival factor and a mitogen is mediated by the lipid kinase phosphatidylinositol 3-kinase (PI3K), since these activities were completely blocked by wortmannin or LY-294002, two structurally dissimilar inhibitors of PI3K. The identification of LPA as a proliferative and anti-apoptotic factor suggests a potential role for this lipid mediator during the injury and/or recovery phases following tubular damage.