GROWTH FACTOR EXPRESSION IN RENAL ENDOTHELIAL CELLS

介导病理性血管的基本机制 肾脏中血管周围细胞的增殖还没有 定义得很清楚。这种增殖可能会导致血管功能不全。 通过高血压患者所见的管腔狭窄 肾硬化症，否则可能会导致 在增生性肾小球疾病中起作用的组织单位。这个 这些研究的目的是确定血管的作用 血管内皮细胞在血管和血管内皮细胞中的作用 血管周围增生。 培养的内皮细胞产生了几个特性良好的 生长因子，包括血小板衍生生长因子(PDGF) 和白介素1(IL-1)，两者都影响生长 参与血管内皮下病变的细胞特性 扩散。拟议的工作将解决体外和体内的 影响这些生长的内皮细胞表达的活体因素 因子和转化生长因子-β(TGF-β)。我们有 新近发现通过培养细胞表达PDGF的活性 人肾微血管内皮细胞将被调控 细胞暴露于凝血酶和转化生长因子β (转化生长因子-β)。我们将量化特定生长的内皮细胞水平 因子信使RNA与生长因子活性的释放 条件培养液作为体外生长因子指标的研究 在不同培养条件和暴露于 与血管增殖部位相关的生化激动剂。 活体研究将使用原位杂交方法来量化 生长因子mRNA在特定细胞类型中的表达水平 肾脏病患者肾组织内皮细胞的变化 以血管和血管周围增殖为特征的疾病。 因此，通过结合体外和体内的方法，这些研究 应能更好地了解影响 肾内皮细胞生长因子的表达及其局部作用 组织生长因子的产生在肾血管和肾脏中的作用 血管周围增生性疾病。

The fundamental mechanisms that mediate pathologic vascular and perivascular cellular proliferation in the kidney are not yet well defined. Such proliferation may cause vascular insufficiency through the lumenal narrowing seen in hypertensive nephrosclerosis, or it may result in the architectural disruption of functioning tissue units as in proliferative glomerulopathies. The goal of these studies is to identify the role of the vascular endothelial cell in producing mediators of vascular and perivascular proliferation. Cultured endothelial cells produce several well-characterized growth factors, including platelet-derived growth factor (PDGF) and interleukin 1 (IL-1), both of which affect the growth properties of cells that participate in pathologic subendothelial proliferation. The proposed work will address the in vitro and in vivo factors that influence endothelial expression of these growth factors and transforming growth factor beta (TGF-beta). We have recently shown the expression of PDGF activity by cultured human renal microvascular endothelial cells to be regulated by exposure of cells to thrombin and transforming growth factor beta (TGF-beta). We will quantify endothelial levels of specific growth factor messenger RNA and release of growth factor activity into conditioned medium as indices of in vitro growth factor expression under varying culture conditions and exposure to biochemical agonists relevant at sites of vascular proliferation. In vivo studies will use in situ hybridization methods to quantify growth factor mRNA expression levels in specific cell types (endothelium) within kidney specimens from patients with renal diseases marked by vascular and perivascular proliferation. Thus by combining in vitro and in vivo approaches, these studies should provide better understanding of the factors influencing renal endothelial growth factor expression and the role that local tissue growth factor production plays in renal vascular and perivascular proliferative diseases.