FATE OF BF 2 EXPRESSING RENAL PROGENITORS

描述：病变肾脏和肾脏中活化的基质细胞的来源。 这些细胞在诱发终末期肾病中所起的作用仍然存在。 难以捉摸，这个顽固的临床问题很难解决，因为 健康肾脏肾间质的起源、分化及功能 人们对此仍然知之甚少。我们证明了有翼螺旋转录因子， BF-2由肾基质祖细胞选择性表达，而BF-2 间质祖细胞的表达对肾上皮细胞的生长和 差异化。在这项建议中，我们将使用BF-2mRNA作为分子标记 鉴定肾间质祖细胞并测试描述 这种细胞群体的起源、分化和命运。在具体目标1中， 逆转录病毒介导的基因将用于分析肾基质细胞的来源 传授血统追踪技术。被标记的血统的不同命运， BF-2在早期鸡胚胎中的表达细胞将被鉴定 通过形态和分子标记分析。特定目标2号将探测BF-2 功能和细胞过程受到BF2缺失的干扰。我们向BF-2展示 空基质细胞经历早熟分化，而对照细胞 下调BF-2的表达与分化程度一致。我们会 确定腺病毒是否介导BF-2的组成性高水平表达 在体外延缓基质分化。我们将检验这一假设 BF-2基因缺失引起的性早分化扰乱颞叶 调控输尿管芽生长的基质因子的表达模式。数据 为今后研究活性物质的来源提供了依据 肾脏基质细胞及其在肾单位退变中的作用 和/或修复。

DESCRIPTION: The origin of activated stromal cells in the diseased kidney and the role that these cells play in precipitating end stage renal disease remains elusive, This recalcitrant clinical problem is difficult to address since the origin, differentiation and function of renal stroma in the healthy kidney remains poorly understood. We show that the Winged Helix transcription factor, BF-2, is selectively expressed by renal stromal progenitors and that BF-2 expressing stromal progenitors are essential for renal epithelial growth and differentiation. In this proposal we will use BF-2 mRNA as a molecular marker to identify renal stromal progenitors and test hypotheses describing the origin, differentiation, and fate of this cell population. In Specific Aim 1, the origin of renal stromal cells will be analyzed by retroviral mediated gene transfer lineage tracing techniques. The differentiated fate of lineage tagged, BF-2 expressing cells present in the early chick embryo will be characterized by morphological and molecular marker analyses. Specific Aim 2 will probe BF-2 function and the cellular processes perturbed by BF2 deletion. We show BF-2 null stromal cells undergo precocious differentiation while control cells down-regulate BF-2 expression coincident with differentiation. We will determine if adenovirus mediated constitutive, high level BF-2 expression delays stromal differentiation in vitro. We will test the hypothesis that precocious differentiation caused by BF-2 deletion perturbs the temporal expression patterns of stromal factors regulating ureteric bud growth. Data generated will provide the basis for future studies on the origin of activated stromal cells in the diseased kidney and their role in nephron degeneration and/or repair.