Schlueter Claudia, Hauke Sven, Flohr Aljoscha M, Rogalla Piere, Bullerdiek Jörn
Center for Human Genetics, University of Bremen, Leobenerstr. ZHG, D-28359 Bremen, Germany
Biochim Biophys Acta. 2003 Oct 20;1630(1):1-6. doi: 10.1016/j.bbaexp.2003.08.008.
The receptor for advanced glycation end products (RAGE) is known to be causally involved in a variety of pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer disease, tumors, and abnormalities associated with diabetes as arteriosclerosis or disordered wound healing. So far, human cDNAs have been characterized encoding for the RAGE receptor and a truncated soluble form lacking the transmembrane and the cytosolic domain. The latter form represents a naturally occurring competitive inhibitor of signalling pathways induced by the membrane-standing RAGE receptor. In order to perform a relative expression analysis of both RAGE forms, an RT-PCR experiment was designed allowing the simultaneous amplification of corresponding transcripts. We were able to identify three novel human RAGE transcripts all encoding truncated soluble forms of RAGE. The relative expression ratios for the full-length RAGE transcript to the sum of its splice-variants encoding the soluble variants varied strongly among the tissues tested. Therefore, the pre-mRNA of RAGE must be subject to regulated alternative splicing activated by extracellular cues of yet unknown cellular signalling pathways. Thus, as deduced from the occurrence at the RNA level, it can be hypothesized that there is a complex RAGE regulation network involving isoforms competing for the binding of ligands.
晚期糖基化终产物受体（RAGE）已知因果性地参与多种病理生理过程，例如免疫/炎症紊乱、阿尔茨海默病、肿瘤以及与糖尿病相关的异常情况，如动脉硬化或伤口愈合紊乱。到目前为止，已对编码RAGE受体以及缺乏跨膜和胞质结构域的截短可溶性形式的人类cDNA进行了表征。后一种形式代表了由膜结合型RAGE受体诱导的信号通路的天然竞争性抑制剂。为了对两种RAGE形式进行相对表达分析，设计了一个RT-PCR实验，以允许同时扩增相应的转录本。我们能够鉴定出三种新的人类RAGE转录本，它们均编码RAGE的截短可溶性形式。在测试的组织中，全长RAGE转录本与其编码可溶性变体的剪接变体之和的相对表达比率差异很大。因此，RAGE的前体mRNA必定受到由未知细胞信号通路的细胞外信号激活的可变剪接调控。因此，从RNA水平的情况推断，可以假设存在一个复杂的RAGE调控网络，其中异构体竞争配体的结合。
