Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney.
Platelet-derived growth factor-C (PDGF-C) is a new member of the PDGF family. Its expression in normal and diseased kidney is unknown. Rabbit antisera were generated against human full-length, core domain, and mouse PDGF-C, and their specificity was confirmed by Western blot analyses. Renal PDGF-C expression was analyzed by immunohistochemistry in normal rats (n = 8), mesangioproliferative anti-Thy 1.1 nephritis (n = 4 each at days 1, 4, 6, and 85), passive Heymann nephritis (PHN, n = 4), puromycin nephrosis (PAN, n = 2), Milan normotensive rats (MN, n = 2), and obese Zucker rats (n = 3). PDGF-C expression was also studied in anti-Thy 1.1 rats treated with PDGF-B aptamer antagonists (n = 5) or irrelevant control aptamers (n = 5). PDGF-C was constitutively expressed in arterial smooth muscle cells and collecting duct epithelial cells. Mesangial PDGF-C was markedly upregulated in anti-Thy 1.1 nephritis in parallel with the peak mesangial cell proliferation. Furthermore, PDGF-CC acted as a potent growth factor for mesangial cells in vitro. Inhibition of PDGF-B via specific aptamers reduced the injury in anti-Thy 1.1 nephritis but did not affect the glomerular PDGF-C overexpression or the mitogenicity of PDGF-CC in vitro. In PHN, PAN, and obese Zucker rats, glomeruli remained negative for PDGF-C despite severe glomerular injury. PDGF-C localized to podocytes at sites of focal and segmental sclerosis in MN. Interstitial PDGF-C expression was increased at sites of fibrosing injury in obese Zucker rats. The use of the different antisera resulted in virtually identical findings. It is concluded that PDGF-C is a novel mesangial cell mitogen that is constitutively expressed in the kidney and specifically upregulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells. PDGF-C may therefore be involved in the pathogenesis of renal scarring.
Eitner
Frank
F
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Ostendorf
Tammo
T
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Van Roeyen
Claudia
C
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Kitahara
Masashi
M
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Li
Xuri
X
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Aase
Karin
K
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Gröne
Hermann-Josef
HJ
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Eriksson
Ulf
U
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
Floege
Jürgen
J
*Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; †Ludwig Institute for Cancer Research, Stockholm, Sweden; and ‡German Cancer Research Institute, DKFZ Heidelberg, Germany.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005355:Fibrosis; D005920:Glomerular Mesangium / Q000166:cytology; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008222:Lymphokines; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D006133:Growth Substances; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C411423:platelet-derived growth factor C