Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression
Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression
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DOI：
10.1042/bj20051573
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发表时间：
2006-05-15
影响因子：
4.1
通讯作者：
Yamamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Harashima, Ai;Yamamoto, Yasuhiko;Yamamoto, Hiroshi
细胞表面RAGE[AGE(晚期糖基化终产物)受体]与糖尿病血管并发症、神经退行性疾病和炎症的发生有关。最近，我们分离到一个人RAGE剪接变异体，它可以作为RAGE配体的诱骗受体，并命名为esRAGE(内源性分泌型RAGE)。在本研究中，我们通过RT(逆转录)-聚合酶链式反应克隆的方法从脑多聚体PolyA(+)(PolyAdamylated)RNA中分离到了与esRAGE类似的基因。该基因通过选择性剪接产生，编码一个334个氨基酸的蛋白和一个信号序列，但缺乏跨膜区。转染法实验表明，该基因实际上是一种新的基因。翻译为推导产生分泌蛋白，在AGE诱导的核因子kappaB(核因子kappa B)激活中充当诱饵。RT-PCR和免疫印迹检测到野生型小鼠脑、肺、肾和小肠中的esRAGE mRNA和蛋白，而RAGE基因缺失的小鼠则未检测到。糖尿病野生型小鼠肾脏组织中esRAGE表达增加。因此，本研究提供了esRAGE的动物同源，以澄清其在健康和疾病中的作用。
The cell-surface RAGE [receptor for AGE (advanced glycation end-products)] is associated with the development of diabetic vascular complications, neurodegenerative disorders and inflammation. Recently, we isolated a human RAGE splice variant, which can work as a decoy receptor for RAGE ligands, and named it esRAGE (endogenous secretory RAGE). In the present study, we have isolated the murine equivalent of esRAGE from brain polysomal poly(A)(+) (polyadenylated) RNA by RT (reverse transcription)-PCR cloning. The mRNA was generated by alternative splicing, and it encoded a 334-amino-acid protein with a signal sequence, but lacking the transmembrane domain. A transfection experiment revealed that the mRNA was actually. translated as deduced to yield the secretory protein working as a decoy in AGE-induced NF-kappa B (nuclear factor kappa B) activation. RT-PCR and immunoblotting detected esRAGE mRNA and protein in the brain, lung, kidney and small intestine of wild-type mice, but not of RAGE-null mice. The esRAGE expression was increased in the kidney of diabetic wild-type mice. The present study has thus provided an animal orthologue of esRAGE for clarification of its roles in health and disease.