GROWTH FACTOR EXPRESSION IN RENAL ENDOTHELIAL CELLS

介导病理性血管病变的基本机制 以及肾脏血管周围细胞增殖 定义明确。 这种增生可能会导致血管功能不全 通过高血压患者的管腔狭窄 肾硬化症，或者它可能会导致建筑破坏， 如增生性肾小球病中的功能组织单位。 的 这些研究的目的是确定血管的作用， 内皮细胞产生血管介质， 血管周围增生 培养的内皮细胞产生几种充分表征的 生长因子，包括血小板衍生生长因子（PDGF） 和白细胞介素1（IL-1），两者都影响生长 参与病理性内皮下 增殖 拟议的工作将解决在体外和在 影响这些生长因子的内皮表达的体内因素 因子和转化生长因子β（TGF-β）。 我们有 最近显示PDGF活性的表达由培养的 人肾微血管内皮细胞受 细胞暴露于凝血酶和转化生长因子β （TGF-β）。 我们将量化内皮细胞的特异性生长 因子信使RNA和释放生长因子活性进入 作为体外生长因子指标的条件培养基 在不同的培养条件和暴露于 与血管增殖部位相关的生化激动剂。 体内研究将使用原位杂交方法来定量 特定细胞类型中的生长因子mRNA表达水平 （内皮细胞）在肾脏病患者的肾脏标本中 以血管和血管周围增生为特征的疾病。 因此，通过结合体外和体内方法，这些研究 应该更好地了解影响因素， 肾局部内皮生长因子的表达及其作用 组织生长因子的产生在肾血管和 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.