Differential expression of platelet‐derived growth factor and transforming growth factor‐β in relation to progression of IgA nephropathy

Abstract

SUMMARY: The role of platelet‐derived growth factor (PDGF) and transforming growth factor‐β1 (TGF‐β1) in relation to mesangial matrix expansion and progressive glomerulosclerosis in IgA nephropathy (IgAN) is not clearly defined. Expression of PDGF B, TGF‐β1, and extracellular matrix proteins in glomeruli was assessed by immunohistochemistry in 42 biopsies with IgAN and six renal biopsies with no detectable abnormalities. The mRNA expression of PDGF B, TGF‐β1, α1(IV) collagen, laminin B1 and fibronectin genes was further evaluated by in situ hybridization in 25 biopsies with IgAN and six controls. In IgAN, the intensity of immunostaining for PDGF B, type IV collagen, laminin and fibronectin, but not for TGF‐β1, was increased in the mesangium compared with controls. The immunoreactivity of PDGF B was closely correlated with that of type IV collagen and laminin. The number of PDGF B mRNA‐, α1(IV) collagen mRNA‐, laminin B1 mRNA‐, and TGF‐β1 mRNA‐expressing cells/glomerular section, but not the number of fibronectin mRNA‐expressing cells, was increased in IgAN compared with controls. The number of PDGF B mRNA‐expressing cells correlated significantly with the percentage of glomerulosclerosis. In the cellular lesions of focal segmental glomerulosclerosis (FSGS), expression of TGF‐β1 protein and mRNA was markedly increased in visceral glomerular epithelial cells (GEC). These results suggest that PDGF B mainly overproduced by mesangial cells may cause mesangial matrix expansion, whereas TGF‐β1 produced by GEC may be related to the formation of FSGS in IgAN. Thus, PDGF B and TGF‐β1 may play differential roles in the pathogenesis of renal fibrosis and the progression of IgAN.