GROWTH FACTORS IN INFANTILE RENAL CYSTIC DISEASE

多囊肾病（PKD）是最常见的遗传性疾病。 肾脏疾病 在人类中，PKD以两种不同的模式遗传， 一种是成人型显性，一种是儿童型隐性。 在这两种形式中， 在这种疾病中，正常的肾组织被无数的囊肿所取代， 内衬有一层增生的上皮，显示出不成熟的表型。 上皮的不成熟可能是由于基因程序性的 不成熟（分化停滞）或诱导状态， 去分化，细胞无法逃脱。 增加 这些未成熟细胞的增殖导致小管增大，即囊肿 阵 我们假设婴儿型PKD是由 集合管段的分化。为了验证这一假设， 将评估收集导管的分化状态， 在遗传和诱导形式发展过程中的几个时间点 婴儿PKD 我们将使用遗传型鼠PKD（C57 BL/6 J-1）。 cpk/cpk）和获得性婴儿型PKD（由糖皮质激素诱导 在新生小鼠和兔中），以确定集合管是否 无论病因如何，囊肿形成具有共同的致病特征。到 评估上皮不成熟，我们将使用核酸杂交， 免疫组织化学染色检测集合管分化。 收集管细胞的其他分化标志物将在 鉴定我们进一步假设，被逮捕的分化， 集合管是由于缺乏成熟因子， 表皮生长因子（EGF） 为了验证这一假设， 将评估EGF基因表达在肾脏的遗传和诱导 婴儿PKD模型。此外，我们将直接确定 EGF诱导集合管细胞分化的能力 体外EGF也将被用于遗传性小鼠和兔子。 和婴儿PKD的诱导形式，以确定EGF是否抑制囊肿 发育并促进体内上皮分化。 我们 预期这些研究将阐明肾上皮细胞的作用， 肾囊肿的病因有哪些

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.