REGULATING UROTHELIAL CELL PROLIFERATING GROWTH FACTORS

本项目的长期目标是了解 生长因子在膀胱尿路上皮细胞增殖中的作用 的 外源性和自分泌性膀胱生长因子对细胞增殖的影响 体外生长可以在确定的条件下使用 正常啮齿动物膀胱上皮的原代培养物。 隔离 正常啮齿类动物膀胱中的生长因子 通过使用肝素亲和层析。 本课题的具体目标是：（1）确定是否正常 啮齿动物膀胱产生自分泌或旁分泌生长因子，（2） 比较膀胱衍生的生长因子和已知的 大小、肝素亲和力、刺激能力等因素 3 T3细胞增殖、血管生成活性、转化生长 因子活性，与EGF和TGF-β受体结合，以及 特异性抗FGF和抗PDGF抗血清的识别，（3） 在无血清培养中检查膀胱尿道炎的反应 外源性生长因子，（4）检查相互作用 膀胱自分泌和外源性生长因子之间的关系 上皮细胞增殖 在这些实验过程中，我们将检验几个假设 关于生长因子参与尿路上皮细胞的性质， 细胞增殖：（a）膀胱尿路上皮生长 受自分泌生长因子调节，（B）外源性生长 膀胱尿路上皮细胞增殖所需的因子， (c)TGF-β抑制膀胱上皮细胞的生长。

The long-term objective of this project is to understand the role of growth factors in proliferation of bladder urothelium. The effects of exogenous and autocrine bladder growth factors on cell growth in vitro can be tested under defined conditions using primary cultures of normal rodent bladder epithelium. Isolation of growth factors from normal rodent bladder will be facilitated by the use of heparin-affinity chromatography. The specific aims of this project are: (1) to determine if normal rodent bladder produces autocrine or paracrine growth factors, (2) to compare bladder-derived growth factors to known growth factors in terms of size, affinity for heparin, ability to stimulate 3T3 cell proliferation, angiogenic activity, transforming growth factor activity, binding to EGF and TGF-beta receptors, and recognition by specific anti-FGF and anti-PDGF antisera, (3) to examine the response of bladder urothelium in serum-free culture to exogenous growth factors, and (4) to examine the interplay between autocrine and exogenous growth factors in bladder epithelial cell proliferation. In the course of these experiments we will test several hypotheses regarding the nature of growth factor involvement in urothelial cell proliferation: (a) that growth of bladder urothelium is regulated by autocrine growth factor(s), (b) that exogenous growth factors are required for proliferation of bladder urothelium, and (c) that TGF-beta inhibits the growth of bladder epithelium.