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。肾脏病急症，月牙状肾小球肾炎（GN），经常导致FSGS。本病以肾小球毛细血管外细胞增生为特征。除了狼疮和血管增生，新月可出现在许多GNs，当出现时，表明严重的疾病进程。在先前的研究中，我们已经表明a)排列在肾小球鲍曼囊内周的细胞，即壁上皮细胞（PECs），在FSGS和新月形成中都起着至关重要的作用；b)小鼠足细胞中血小板衍生生长因子(PDGF)-DD过表达可导致月牙形和血管间增生性GN；c) PDGFs是肾小球细胞的强效分裂原和促纤维化因子；d)肾小球中PDGF受体承载细胞主要包括肾小球内皮细胞和PECs。在这里，我们假设PDGFs是重要的有丝分裂原和pec的纤维化激活剂，从而介导月牙形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。这些将用于月牙形GN和FSGS模型。原代小鼠epecs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.