Clinical assessment of the significance of platelet-derived growth factor in patients with immunoglobulin A nephropathy.
To examine the role of platelet-derived growth factor (PDGF) in the pathogenesis of IgA nephropathy (IgAN), we investigated the expression of PDGF and the PDGF receptor in glomeruli with immunohistochemistry, the plasma levels of PDGF with ELISA, and the expression of PDGF in peripheral blood monocytes (PBMCs) with reverse transcription polymerase chain reaction (RT-PCR). We also assessed the effect of corticosteroid therapy on the plasma levels of the PDGF B-chain. At the time of kidney biopsy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was upregulated in patients with IgAN. In addition, the plasma concentration of the PDGF B-chain was significantly higher in patients with IgAN than in normal subjects. Moreover, mRNA expression of PDGF beta-chain in PBMCs was up-regulated in patients with IgAN when compared with other patients with glomerulonephritis. We divided the patients into two groups according to the grade of urinary protein excretion (U[p]) after corticosteroid therapy. In patients in group 1 in whom U(p) was decreased by more than 50% or 1 gm/day after corticosteroid therapy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was up-regulated. Finally, corticosteroid therapy decreased the plasma levels of PDGF B-chain in patients in group 1. Up-regulation of the PDGF B-chain and beta receptor in the glomeruli, elevated plasma levels of PDGF B-chain, and increased expression of PDGF mRNA in PBMCs could be associated with the pathogenesis of IgAN. The plasma concentration of PDGF B-chain may be a useful marker for patients with IgAN who would be responsive to corticosteroid therapy.
Naito
T
T
Department of Medicine, Kidney Center, Tokyo Women's Medical College, Shinjuku-ku, Japan.
Nitta
K
K
Ozu
H
H
Tsuchiya
K
K
Matsugami
K
K
Honda
K
K
Yumura
W
W
Nihei
H
H
D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D017931:DNA Primers; D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011239:Prednisolone; D003404:Creatinine; D017479:Receptors, Platelet-Derived Growth Factor