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Analysis on the lineage of adrenocortical cells with 3-dimentional arrangement

肾上腺皮质细胞三维谱系分析

基本信息

批准号：
15570052
负责人：
MITANI Fumiko
金额：
$ 2.37万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The adrenal cortex is composed of two functionally and ontogenetically different tissues, the medulla and the cortex. The cortex of mesodermal origin further separates into three concentric zones with specific functions : the zona glomerulosa(zG), the zona fasciculata (zF) and the zona reticularis (zR). Formerly we discovered another zone(undifferentiated cell zone : zU) between zG and zF ; cells in the layer are thought to be stem cells for adrenocortical cells as judged by their inability to express zone-specific steroidogenic enzymes and the behavior of proliferating cells around the zone. We then established such cell-lines(zU-cell line). We tried to transplant the zU cells to the kidney of scid mice, but so far we have not succeeded yet. This study was aimed to investigate the lineage of adrenocortical cells and mechanisms of the maintenance of cortical zones.A new secretory protein(designated later as adrenocortical zonation factor 1 : AZ-1) was identified in the cell line described above by subtractive hybridization. The protein contained a secretory signal, EGF-like repeats, and a proteolytically inactive catepsin B- related sequence. The AZ-1 mRNA was detected only in zU and zG. Interestingly the expression of AZ-1 mRNA in adrenocortical cells was inversely correlated with that of P45011β mRNA. AZ-1 protein, on the other hand, was observed in extracellular portions of whole drenal cortex ; it colocalizes with laminin, collagen, and fibronectin which associate with blood vessels. During development of the cortex, AZ-1 always colocalized with those extracellular matrix. The migration and differentiation of cortical cells may occur along extracellular matrix with the aid of AZ- I.

肾上腺皮质由两个功能和个体发育不同的组织组成，即髓质和皮质。起源于中胚层的皮质进一步分为三个具有特定功能的同心区：球状带(ZG)、束状带(ZF)和网状带(ZR)。以前，我们在ZG和ZF之间发现了另一个区域(未分化细胞区：ZU)；该层中的细胞被认为是肾上腺皮质细胞的干细胞，因为它们不能表达区域特异性类固醇生成酶，以及区域周围增殖细胞的行为。然后我们建立了这样的细胞系(zu-细胞系)。我们试图将ZU细胞移植到SCID小鼠的肾脏，但到目前为止还没有成功。本研究旨在探讨肾上腺皮质细胞的谱系及其维持皮质带的机制。通过消减杂交，在上述细胞系中鉴定出一种新的分泌蛋白(后来命名为肾上腺皮质分区因子1：AZ-1)。该蛋白含有一个分泌信号、EGF样重复序列和一个蛋白水解性的儿茶素B相关序列。AZ-1mRNA仅在ZU和ZG中检测到。有趣的是，AZ-1m RNA在肾上腺皮质细胞中的表达与P45011βm RNA的表达呈负相关。另一方面，AZ-1蛋白存在于整个肾上腺皮质的胞外部分，它与与血管相关的层粘连蛋白、胶原和纤维连接蛋白共存。在皮质发育过程中，AZ-1总是与这些细胞外基质共定位。在AZ-I的帮助下，皮质细胞可能沿细胞外基质发生迁移和分化。