PDGF-D: a novel mediator of mesangioproliferative glomerulonephritis

Abstract

In view of the increasing number of patients with end-stage renal disease (ESRD), new approaches to common underlying diseases such as mesangioproliferative glomeruionephritis, including igA nephropathy, are urgently needed. Whereas the role of platelet-derived growth factor (PDGF) B-chain (PDGF-B) in mediating mesangloproliferative changes is well established, the role of PDGF D-chain (PDGF-D) has only recently been elucldated. Like PDGF-B, PDGF-D signals through the POGF β-receptor and therefore shares a number of biological activities with PDGF-B. Recent studies have shown that PDGF-D induces mesangial cell proliferation in vitro and is overexpressed in mesangioproliferative giomerulonephritis in vivo. In addition, hepatic transfection with a PDGF-D expression plasmid induced prominent mesangioproliferative nephritis in mice, whereas antagonism of PDGF-D in a rat model of mesangioproliferative disease ameliorated the renal changes. These observations establish PDGF-D, along with PDGF-B, as an important mediator of mesangioproliferative nephritis in vivo and suggest that it may be an attractive therapeutic target. in addition, preliminary observations suggest that PDGF-D may also contribute to secondary renal changes that characterize progressive renal failure, i.e., tubulointerstitial fibrosis.