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Identification of Novel ACE2 homologue, collectrin, and its role in renal organogenesis and progressive renal failure.

新型 ACE2 同源物 Collectrin 的鉴定及其在肾器官发生和进行性肾衰竭中的作用。

基本信息

批准号：
14571025
负责人：
WADA Jun
金额：
$ 1.79万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571025/
关键词：
collectrin ACE2 HNF-1β renal organogenesis glomerulosclerosis

项目摘要

Collectrin, a novel homologue of angiotensin converting enzyme-related carboxypeptidase (ACE2), was identified in 5/6 ablated kidneys at hypertrophic phase (Zhang H et al. J Biol Chem 276(20),17132-17139,2001). By using an animal model of partial nephrectomy, several differentially expressed genes were isolated by the PCR-based cDNA-subtraction method (Zhang H et al. Kidney Int 56(2),549-558,1999). Because one of these genes was kidney-specific and highly localized to the collecting ducts, it was designated as collectrin. The sequence analyses revealed that collectrin with 222 amino acids has an apparent signal peptide and a transmembrane domain (black box in figure shown below) ; the sequence is conserved in mouse, rat and human and shared 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular and cytosolic domains of ACE2 (white box in figure), however, unlike ACE and ACE2, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. Interestingly, ACE2 and collectrin are located close to each other in the same chromosomal region (Xp22) and whereas ACE is located chromosome 17. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts and immunohistochemistry shows it is localized to the luminal surface and cytoplasm of collecting ducts.

Collectrin是血管紧张素转换酶相关羧肽酶(ACE2)的一种新的同系物，在5/6肥厚期的消融肾脏中被发现(Zhang H et al.生物化学杂志276(20)，17132-17139,2001)。通过建立肾部分切除的动物模型，采用基于聚合酶链式反应的cDNA消减方法分离了几个差异表达基因(Zhang H et al.肾国际56(2)，549-558,1999)。因为这些基因中的一个是肾脏特异的，并且高度定位于集合管，所以被指定为集合素。序列分析表明，含有222个氨基酸的集合素具有明显的信号肽和跨膜结构域(如下图所示的黑框)；该序列在小鼠、大鼠和人中保守，有81.9%的同源性。人凝集素与ACE2的胞外和胞内非催化结构域(如图中的白框)有47.8%的同源性，但与ACE和ACE2不同的是，它缺乏活性的二肽基羧肽酶催化结构域。有趣的是，ACE2和Colltrin位于同一染色体区域(Xp22)，而ACE位于17号染色体上。Colltrin mRNA转录本仅在肾脏表达。原位杂交显示其在肾脏集合管中有表达，免疫组织化学显示其定位于集合管的管腔表面和胞浆。