Glomerular cross-talk between podocytes and parietal epithelial cells: the role of platelet-derived growth factors (PDGFs)

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Glomerulosclerosis (FSGS) is the end-point of all progressive glomerular diseases. The nephrologicalemergency, crescentic glomerulonephritis (GN), frequently leads to FSGS. This disease ischaracterized by the formation of glomerular extracapillary cellular proliferates. Apart from lupus andvasculitides, crescents can occur in many GNs and, when present, indicate a severe disease course.In prior studies we have shown that a) the cells lining the inner circumference of the glomerularBowman’s capsule, i.e. parietal epithelial cells (PECs), are crucially involved in both FSGS andcrescent formation; b) that platelet-derived growth factor (PDGF)-DD overexpression in podocytes inmice leads to crescentic and mesangioproliferative GN; c) that PDGFs are potent mitogens andprofibrotic factors for glomerular cells; d) that in glomeruli PDGF receptor-bearing cells mainly includemesangial cells and PECs. Here, we hypothesize, that PDGFs are important mitogens and profibroticactivators of PECs, thereby mediating both crescentic GN and FSGS. To address this hypothesis, wewill use our own unique tools including PDGF-DD deficient mice, PDGF-DD neutralizing antibody, andPEC reporter mice. These will be employed in models of crescentic GN and FSGS. Primary murinePECs will be used in in vitro experiments.