Glomerular expression of platelet-derived growth factor (PDGF)-A, -B chain and PDGF receptor-alpha, -beta in human diabetic nephropathy.

Abstract

Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN. We examined open renal biopsies of 20 type 2 diabetic patients with DN, and 10 normal human kidneys (NHK). Histopathologically, the severity of DN was classified as grade I (DN I, n = 10; mild mesangial expansion) or grade II (DN II, n = 10; moderate mesangial expansion). We evaluated the expression and localization of PDGF-A, -B, and PDGFR-Alpha, -Beta using in situ hybridization, and quantified PDGF and PDGFR mRNA expression by counting all nuclei, and nuclei surrounded by PDGF-positive cytoplasm and PDGFR-positive cytoplasm, in at least ten randomly selected cross-sections of nonsclerotic glomeruli. In all glomeruli, PDGF and PDGFR mRNAs were expressed mainly in glomerular resident cells, predominantly glomerular mesangial and epithelial cells. The percentages of cells positive for PDGF-A and PDGFR-Alpha mRNA in DN were similar to those in NHK. In contrast, the percentages of PDGF-B and PDGFR-Beta mRNA-positive cells in DN were significantly higher than those in NHK, and were significantly higher in DN I than in DN II: The percentages of cells positive for PDGF-B correlated with the PDGFR-Beta mRNA level. Our results suggest that the expression of PDGF-B and PDGFR-Beta is an important factor in histologically early glomerular lesions of DN. Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDGF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN.