The role of PDGF-D in mesangioproliferative glomerulonephritis.
In view of increasing numbers of patients with end-stage renal disease (ESRD), new approaches to common underlying diseases, such as mesangioproliferative glomerulonephritis, including IgA nephropathy, are urgently needed. Whereas the role of the platelet-derived growth factor (PDGF) B chain in mediating mesangioproliferative changes is well established, the role of the PDGF-D chain has only recently been elucidated. The PDGF-D chain, like PDGF-B, signals through the PDGF beta-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 glomerulonephritis in vivo. Hepatic transfection with an adenoviral vector expressing PDGF-D induced prominent mesangioproliferative nephritis in mice, whereas antagonism of PDGF-D in a rat model of mesangioproliferative disease ameliorated the renal changes. These four observations establish PDGF-D, like -B, as an important mediator of mesangioproliferative nephritis in vivo and suggest that it may be an attractive therapeutic target. In addition, first observations suggest that PDGF-D may also contribute to secondary renal changes that characterize progressive renal failure, i.e. tubulointerstitial fibrosis.
Floege
Jürgen
J
Division of Nephrology and Immunology, RWTH University of Aachen, Aachen, Germany. Juergen.Floege@rwth-aachen.de
van Roeyen
Claudia
C
Boor
Peter
P
Ostendorf
Tammo
T
D000818:Animals; D005922:Glomerulonephritis, IGA / Q000503:physiopathology* / Q000628:therapy; D015432:Glomerulonephritis, Membranoproliferative / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*
D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor