Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane.
Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane.
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DOI：
10.1038/srep44266
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发表时间：
2017-03-09
影响因子：
4.6
通讯作者：
Ishida S
中科院分区：
文献类型：
--
作者：
Dong Y;Kanda A;Noda K;Saito W;Ishida S
受体相关的促肾素系统（receptor -associated prorenin system， RAPS）是指促肾素结合（pro）肾素受体[(P)RR]双重激活组织肾素-血管紧张素系统（RAS）和通过(P)RR激活RAS独立信号的致病机制。本研究的目的是确定RAPS与特发性视网膜前膜（iERM）的关系。逆转录- pcr检测结果显示，在iERM组织和人胆管神经胶质细胞系中，RAPS组分包括(P)RR和Ang II型1受体（AT1R）的表达。双标记分析表明，(P)RR和AT1R分别在胶质纤维酸性蛋白（胶质细胞的标志物）阳性细胞中检测到，并与prorenin和血管紧张素原共定位。<s:1>神经胶质细胞给予prorenin可增强成纤维细胞生长因子2的mRNA表达，而应用Ang II可刺激胶质细胞系源性神经营养因子、神经生长因子和转化生长因子-β1的表达。prorenin或Ang II诱导的这些表达水平分别被(P)RR或AT1R阻断逆转。免疫荧光显示(P)RR和AT1R在体外与上调基因的产物共定位。本研究结果提示RAPS参与了iERM的发病机制。
Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively. Administration of prorenin to Müller glial cells enhanced mRNA expression of fibroblast growth factor 2, while Ang II application stimulated the expression of glial cell line-derived neurotrophic factor, nerve growth factor, and transforming growth factor-β1. These expression levels induced by prorenin or Ang II were reversed by (P)RR or AT1R blockade, respectively. Immunofluorescence revealed tissue co-localization of (P)RR and AT1R with the products of the upregulated genes in vitro. The present findings suggest the involvement of RAPS in the pathogenesis of iERM.