Uchide Tsuyoshi, Saida Kaname
Laboratory of Toxicology, Department of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University, 35-1 Higashi 23-bancho, Towada, Aomori 034-8628, Japan.
Exp Biol Med (Maywood). 2006 Jun;231(6):997-1000.
Endothelin (ET)-1 is involved in the pathophysiology of various renal disorders, promoting renal cellular proliferation and extracellular matrix protein accumulation, and, thus, diminishing fundamental renal function, including filtration. To determine whether ET-1 and ET-2 play a role in feline chronic renal failure, we analyzed the messenger RNA (mRNA) expression of the prepro-ET (PPET )-1 and PPET-2 genes in affected cat kidney after molecular cloning of full-length PPET-2 complementary DNA (cDNA). Conceptual analysis of the primary structure of cat PPET-2 based on the cloned sequence demonstrated that the putative regions corresponding to a mature peptide and peptidase processing sites are present in cat PPET-2. Homology analysis showed that the similarity of the cat PPET-2 amino acid sequence with those from human, mouse, rat, rabbit, dog, ferret, cow, and horse was 73.0%, 68.6%, 69.1%, 76.4%, 81.2%, 83.1%, 76.3%, and 79.2%, respectively. Analysis of PPET-1 and PPET-2 mRNA in cat by reverse transcription polymerase chain reaction showed upregulated expression of both genes in kidneys affected by renal failure.
内皮素（ET）-1参与多种肾脏疾病的病理生理过程，促进肾细胞增殖和细胞外基质蛋白积聚，从而损害包括滤过功能在内的基本肾功能。为了确定ET-1和ET-2在猫慢性肾衰竭中是否起作用，我们在全长PPET-2互补DNA（cDNA）分子克隆后，分析了患病猫肾脏中前体ET（PPET）-1和PPET-2基因的信使核糖核酸（mRNA）表达。基于克隆序列对猫PPET-2一级结构的概念分析表明，猫PPET-2中存在与成熟肽和肽酶加工位点相对应的假定区域。同源性分析显示，猫PPET-2氨基酸序列与人类、小鼠、大鼠、兔子、狗、雪貂、牛和马的氨基酸序列的相似性分别为73.0%、68.6%、69.1%、76.4%、81.2%、83.1%、76.3%和79.2%。通过逆转录聚合酶链反应分析猫体内的PPET-1和PPET-2 mRNA，结果显示这两个基因在肾衰竭患病肾脏中的表达均上调。
