LPA as a Determinant of Mesangial Growth and Apoptosis

Mesangial cell proliferation is a prominent feature of progression in many forms of renal diseases, including immunoglobulin A nephropathy, lupus nephritis, hemolytic uremic syndrome, and diabetic nephropathy. Plateletderived growth factor (PDGF) has received much attention as the major mediator of mesangial cell proliferation by autocrine/paracrine mechanisms involving up-regulation of mesangial PDGF and its receptor on mesangial cells. In this review, we wish to spotlight lysophosphatidic acid (LPA), which in combination with PDGF, undoubtedly plays a key role as an autocrine and paracrine mediator in regulating mesangial cell growth. We not only showed that PDGF acts as a bimodal molecule for mesangial cells, inducing mesangial cell proliferation and death simultaneously, but also showed that LPA is a survival factor suppressing PDGF-induced mesangial cell death, thereby remarkably enhancing mesangial mitogenic response by PDGF. We believe that a better understanding of the mechanisms of mesangial cell proliferation by the combined action of PDGF and LPA could lead to novel diagnostic as well as therapeutic strategies, and thus help to better control proliferative glomerulonephritis.