DEVELOPMENTAL PATTERNS OF PDGF B-CHAIN, PDGF-RECEPTOR, AND ALPHA-ACTIN EXPRESSION IN HUMAN GLOMERULOGENESIS

Expression of PDGF B-chain and the PDGF receptor beta-subunit (PDGFR-beta) 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 PDGFR-beta 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 PDGFR-beta 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 (alpha-smooth muscle actin), indicate that the PDGF B-chain and PDGFR-beta 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 alpha-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 PDGFR-beta. The upregulation of mesangial PDGF, PDGFR-beta, and alpha-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.