OXIDANT/ANTIOXIDANT EFFECTS OF TGF-B1 ON LUNG CELLS

描述：（改编自申请人的摘要和具体目标。） 细胞因子转化生长因子β-1（TGF-β 1）已被广泛应用于临床。 与某些肺部疾病的发病机制有关， 肺血管损伤和重塑。 然而，其机制 对细胞的作用尚不清楚。 该申请假设TGF-β 1 可能会影响肺血管系统和可能的其他组成部分， 通过肺内氧化剂/抗氧化剂系统的改变 细胞具体目的是：（1）评价“亲”的机制， TGF-β 1对内皮细胞的“氧化”作用; 2）测定TGF-β 1对内皮细胞的“氧化”作用。 TGF-β 1减少细胞谷胱甘肽的机制; 3）更好地定义 TGF-β 1对细胞Cu、Zn-和Mn-SOD的调节作用; 4） 评估TGF-β 1使其氧化剂/抗氧化剂永久存在的概念 通过自分泌作用对内皮细胞产生影响， 由细胞谷胱甘肽含量调节。 这些研究可以提供 TGF-β 1对肺血管内皮细胞作用的新认识 细胞，特别是，并可能提供更广泛的解释， TGF-β 1对细胞的作用。 它们也可能有助于更好地 在细胞水平上了解某些肺疾病的发病机制 以组织损伤和重塑为特征的疾病，从而导致 新的治疗选择

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The cytokine transforming growth factor beta-1 (TGF-b1) has been implicated in the pathogenesis of certain lung diseases associated with pulmonary vascular injury and remodeling. However, its mechanism of action on cells is not known. The application hypothesizes that TGF-b1 may affect the pulmonary vasculature and possibly other components of the lung through alterations in oxidant/anti-oxidant systems within lung cells. The Specific Aims are to: 1) evaluate the mechanism of the "pro- oxidant" effect of TGF-b1 on endothelial cells; 2) determine the mechanism by which TGF-b1 reduces cellular glutathione; 3) better define the regulatory role of TGF-b1 on cellular Cu, Zn- and Mn-SOD; and 4) evaluate the concept that TGF-b1 perpetuates its oxidant/anti-oxidant effects on endothelial cells through an autocrine action that is regulated by the cellular glutathione content. The studies may provide new insights into the actions of TGF-b1 on pulmonary vascular endothelial cells, in particular, and may provide a broader interpretation of the action of TGF-b1 on cells in general. They may also help to better understand at the cellular level the pathogenesis of certain lung diseases characterized by tissue injury and remodeling, thereby leading to new therapeutic options.