PDGF-C expression in the developing and normal adult human kidney and in glomerular diseases.
PDGF-C is a new member of the PDGF-family and has recently been identified as a rat mesangial cell mitogen. Its expression and function in human kidneys is unknown. Localization of PDGF-C protein was analyzed by immunohistochemistry using a rabbit polyclonal antibody directed against the core-domain of PDGF-C in human fetal kidneys (n = 8), normal adult human kidneys (n = 9), and in renal biopsies of patients with IgA nephropathy (IgAN, n = 31), membranous nephropathy (MGN, n = 8), minimal change disease (MC, n = 7), and transplant glomerulopathy (TxG, n = 12). Additionally, PDGF-C mRNA was detected in microdissected glomeruli by real-time RT-PCR in cases of normal adult kidneys (n = 7), IgAN (n = 27), MGN (n = 11), and MC (n = 13). In the fetal kidney, PDGF-C localized to the developing mesangium, ureteric bud epithelium, and the undifferentiated mesenchyme. In the adult kidney, PDGF-C was constitutively expressed in parietal epithelial cells of Bowman's capsule, tubular epithelial cells (loops of Henle, distal tubules, collecting ducts), and in arterial endothelial cells. A marked upregulation of glomerular PDGF-C protein was seen in MGN and TxG with a prominent positivity of virtually all podocytes. In MC, PDGF-C localized to podocytes in a more focal distribution. In MGN, increased glomerular PDGF-C protein expression was due to increased mRNA synthesis as a 4.3-fold increase in PDGF-C mRNA was detected in microdissected glomeruli from MGN compared with normal. PDGF-C protein was additionally expressed in individual mesangial cells in TxG. Finally, upregulated PDGF-C protein expression was detected within sclerosing glomerular and fibrosing tubulointerstitial lesions in individual cases from all analyzed groups. We conclude that PDGF-C is constitutively expressed in the human kidney and is upregulated in podocytes and interstitial cells after injury/activation of these cells.
Eitner
Frank
F
Division of Nephrology and Immunology, Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany. feitner@ukaachen.de
Ostendorf
Tammo
T
Kretzler
Matthias
M
Cohen
Clemens D
CD
Eriksson
Ulf
U
Gröne
Hermann-Josef
HJ
Floege
Jürgen
J
D000328:Adult; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005922:Glomerulonephritis, IGA / Q000473:pathology / Q000503:physiopathology; D015433:Glomerulonephritis, Membranous / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000473:pathology / Q000502:physiology*; D008222:Lymphokines; D009402:Nephrosis, Lipoid / Q000473:pathology / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C411423:platelet-derived growth factor C