GROWTH FACTORS IN INFANTILE RENAL CYSTIC DISEASE

多囊肾病(PKD)是最常见的遗传传播疾病。 肾脏疾病。在人类中，PKD以两种不同的方式遗传，一种是 成体，显性类型和婴幼儿，隐性类型。在两种形式的 这种疾病，正常的肾脏组织被无数的囊肿所取代 由显示未成熟表型的增生性上皮排列。 上皮不成熟可能是由一种遗传程序化引起的 不成熟(分化受阻)或诱导状态 细胞无法逃脱的去分化。增加了 这些未成熟细胞的增殖会导致肾小管增大，即囊肿 队形。我们假设婴儿PKD是由被捕引起的 集合管段的分化。为了检验这一假设，我们 将评估收集管的分化状态 遗传型和诱导型发展过程中的几个时间点 婴儿型多发性硬化症。我们将使用遗传型小鼠PKD(C57BL/6J- CPK/CPK)和获得性婴儿PKD(糖皮质激素诱导) 在新生小鼠和兔子中)，以确定集合管是否 无论病因如何，囊性病变都有共同的致病特征。至 评估上皮不成熟，我们将使用核酸杂交和 集合管分化的免疫组织化学染色。 用于收集导管细胞的其他分化标记将是 已确认身份。我们进一步假设，受阻的分化 收集管是由于没有成熟因子， 尤其是表皮生长因子(EGF)。为了检验这一假设，我们 将评估EGF基因在遗传性和诱导性肾脏中的表达 婴幼儿PKD模型的建立。此外，我们还将直接确定 表皮生长因子诱导集合管细胞分化的能力 体外培养。EGF也将用于遗传性疾病的小鼠和兔子 和诱导婴儿PKD的形式以确定EGF是否抑制囊性 在体内发育并促进上皮分化。我们 预期这些研究将阐明肾上皮细胞的作用 不成熟在肾囊肿发病机制中的作用

Polycystic kidney disease (PKD) is the most common genetically transmitted renal disease. In humans, PKD is inherited in two different modes, an adult, dominant form and an infantile, recessive type. In both forms of this disease, normal kidney tissue is replaced by innumerable cysts which are lined by a hyperplastic epithelium displaying an immature phenotype. The epithelial immaturity could arise from either a genetically programmed immaturity (arrested differentiation) or an induced state of dedifferentiation from which the cells cannot escape. Increased proliferation by these immature cells causes tubule enlargement, i.e. cyst formation. We hypothesize that infantile PKD is caused by arrested differentiation of the collecting duct segment. To test this hypothesis we will evaluate the state of differentiation of the collecting ducts at several time points during the development of inherited and induced forms of infantile PKD. We will use an inherited type of murine PKD (C57BL/6J- cpk/cpk) and an acquired type of infantile PKD (induced by glucocorticoids in neonatal mice and rabbits), to determine if collecting duct cystogenesis has common pathogenic features irrespective of etiology. To evaluate epithelial immaturity, we will use nucleic acid hybridization and immunohistochemistry with probes of collecting duct differentiation. Additional differentiation markers for collecting duct cells will be identified. We further hypothesize that the arrested differentiation in the collecting duct is due to the absence of a maturation factor, specifically epidermal growth factor (EGF). To test this hypothesis we will evaluate EGF gene expression in the kidneys of inherited and induced models of infantile PKD. In addition, we will directly determine the capability of EGF to induce collecting duct cells to differentiate in vitro. EGF will also be administered to mice and rabbits with inherited and induced forms of infantile PKD to determine if EGF inhibits cyst development and promotes epithelial differentiation in vivo. We anticipate that these studies will elucidate the role of renal epithelial immaturity in the pathogenesis of renal cysts.