Abstract
Platelet-derived growth factor (PDGF) B-chain and PDGF receptor beta (PDGFR beta) are essential for glomerulogenesis. Mice deficient in PDGF B-chain or PDGFR beta exhibit an abnormal glomerular phenotype characterized by total lack of mesangial cells. In this study, we localized PDGFR beta in the developing rat kidney and explored the biological effects of PDGF in metanephric mesenchymal cells in an attempt to determine the mechanism by which PDGF regulates mesangial cell development. Immunohistochemical and in situ hybridization studies of rat embryonic kidneys reveal that PDGFR beta localizes to undifferentiated metanephric mesenchyme and is later expressed in the cleft of the comma-shaped and S-shaped bodies and in more mature glomeruli in a mesangial distribution. We also isolated and characterized cells from rat metanephric mesenchyme. Metanephric mesenchymal cells express vimentin and alpha-smooth muscle actin but not cytokeratin. These cells also express functional PDGFR beta, as demonstrated by autophosphorylation of the receptor as well as activation of phosphatidylinositol 3 kinase in response to PDGF B-chain homodimer. PDGF B-chain also induces migration and proliferation of metanephric mesenchymal cells. Taken together with the fact that PDGF B-chain is expressed in the glomerular epithelium and mesangial area, as demonstrated in the human embryonic kidney, we suggest that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangial area. PDGF B-chain also likely stimulates proliferation of mesangial cell precursors in an autocrine fashion once these cells migrate to the glomerular tuft.
Highlights
Platelet-derived growth factor (PDGF) B-chain and PDGF receptor  (PDGFR ) are essential for glomerulogenesis
Taken together with the fact that PDGF Bchain is expressed in the glomerular epithelium and mesangial area, as demonstrated in the human embryonic kidney, we suggest that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangial area
In human embryo at 54 –105 days of gestation, immunohistochemical studies demonstrated that PDGFR  is expressed in the undifferentiated metanephric mesenchyme and in maturing glomeruli, whereas platelet-derived growth factor (PDGF) B-chain is expressed in epithelial cells and the mesangium of maturing glomeruli [1]
Summary
Vol 275, No 13, Issue of March 31, pp. 9527–9533, 2000 Printed in U.S.A. Platelet-derived Growth Factor Receptor  Regulates Migration and DNA Synthesis in Metanephric Mesenchymal Cells*. In human embryo at 54 –105 days of gestation, immunohistochemical studies demonstrated that PDGFR  is expressed in the undifferentiated metanephric mesenchyme and in maturing glomeruli, whereas platelet-derived growth factor (PDGF) B-chain is expressed in epithelial cells and the mesangium of maturing glomeruli [1]. This spatial and temporal distribution of PDGF B-chain and PDGFR  suggests a role for PDGF in the development of glomerular cells, including mesangial cells. Directed migration of a subset of mesenchymal stem cells into the cleft of the maturing glomerulus, where PDGF BB is synthesized, and subsequent proliferation are potential mechanisms by which PDGF BB acting on PDGFR  contributes to mesangial cell development
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