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

肾小球硬化（FSGS）是所有进行性肾小球疾病的终点。新月体肾小球肾炎（GN）是一种肾脏急症，常导致FSGS。本病以肾小球毛细血管外细胞增生物的形成为特征。除狼疮和血管炎外，新月体也可发生在许多肾小球肾炎中，当新月体出现时，表明病程严重。在先前的研究中，我们已经表明：a）肾小球Bowman囊内周的细胞，即壁上皮细胞（佩奇），在FSGS和新月体的形成中起关键作用; B）小鼠足细胞中血小板衍生生长因子（PDGF）-DD过表达导致新月体和系膜增生性GN;（4）肾小球内PDGF受体阳性细胞主要为系膜细胞和佩奇。在这里，我们假设，PDGF是重要的有丝分裂原和佩奇的促纤维化激活剂，从而介导新月体GN和FSGS。为了解决这一假设，我们将使用我们自己独特的工具，包括PDGF-DD缺陷小鼠，PDGF-DD中和抗体和PEC报告小鼠。这些将用于新月体GN和FSGS模型。原代鼠PEC将用于体外实验。

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.