Developmental patterns of PDGF B-chain, PDGF-receptor, and α-actin expression in human glomerulogenesis

Abstract

Expression of PDGF B-chain and the PDGF receptor β-subunit (PDGFRβ) is detected immunocytochemically during the development of glomeruli in human kidneys of 54 to 105 days gestational age. During the early stages (vesicular, comma-shape and S-shape) of glomerulogenesis, PDGF B-chain is localized to differentiating epithelium of the glomerular vesicle, while PDGFRβ is expressed in the undifferentiated metanephric blastema, vascular structures, and interstitial cells. During this stage PDGF may be acting as a paracrine growth factor and as a chemoattractant acting to recruit mesangial progenitor cells into the developing glomerulus. As the glomerular tuft forms, both PDGF B-chain and PDGFRβ can be detected in an arboreal pattern radiating from the hilus of the glomerular tuft. Immunocytochemical studies using markers specific to endothelium (Ulex europaeus I lectin, Factor VIII related antigen), and smooth muscle (α-smooth muscle actin), indicate that the PDGF B-chain and PDGFRβ are both expressed primarily by mesangial cells. During this stage, PDGF may be acting primarily to provide an autocrine factor to mediate further mesangial cell proliferation. Glomerular expression of α-smooth muscle actin is limited to later stages of glomerulogenesis; at these stages the pattern of expression is similar to that of PDGF-B chain and PDGFRβ. The upregulation of mesangial PDGF, PDGFRβ, and α-smooth muscle actin expression that has been identified in some disease states in both humans and experimental animals appears to represent a recapitulation of this normal developmental process.