title: PDGF-C mediates glomerular capillary repair.
abstract: Glomerular endothelial cell injury is a key component of a variety of diseases. Factors involved in glomerular endothelial cell repair are promising therapeutic agents for such diseases. Platelet-derived growth factor (PDGF)-C has pro-angiogenic properties; however, nothing is known about such functions in the kidney. We therefore investigated the consequences of either PDGF-C infusion or inhibition in rats with mesangioproliferative glomerulonephritis, which is accompanied by widespread glomerular endothelial cell damage. We also assessed the role of PDGF-C in a mouse model of thrombotic microangiopathy as well as in cultured glomerular endothelial cells. PDGF-C infusion in nephritic rats significantly reduced mesangiolysis and microaneurysm formation, whereas glomerular endothelial cell area and proliferation increased. PDGF-C infusion specifically up-regulated glomerular fibroblast growth factor-2 expression. In contrast, antagonism of PDGF-C in glomerulonephritis specifically reduced glomerular endothelial cell area and proliferation and increased mesangiolysis. Similarly, PDGF-C antagonism in murine thrombotic microangiopathy aggravated the disease and reduced glomerular endothelial area. In conditionally immortalized glomerular endothelial cells, PDGF-C was mitogenic and induced a 27-fold up-regulation of fibroblast growth factor-2 mRNA. PDGF-C also exerted indirect pro-angiogenic effects, since it induced endothelial cell mitogens and pro-angiogenic factors in mesangial cells and macrophages. These results identify PDGF-C as a novel, potent pro-angiogenic factor in the kidney that can accelerate capillary healing in experimental glomerulonephritis and thrombotic microangiopathy.
authors.affiliation: Division of Nephrology and Immunology, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. boor@email.cz
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.forename: Claudia R C
authors.initials: CR
authors.lastname: van Roeyen
authors.forename: Uta
authors.initials: U
authors.lastname: Kunter
authors.forename: Luigi
authors.initials: L
authors.lastname: Villa
authors.forename: Eva
authors.initials: E
authors.lastname: Bücher
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
authors.forename: Christian P M
authors.initials: CP
authors.lastname: Hugo
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Simon C
authors.initials: SC
authors.lastname: Satchell
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mathieson
authors.forename: Frank
authors.initials: F
authors.lastname: Eitner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009393:Nephritis / Q000139:chemically induced / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D057049:Thrombotic Microangiopathies / Q000378:metabolism / Q000473:pathology
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C; D016222:Fibroblast Growth Factor 2