An angiogenic role for adrenomedullin in choroidal neovascularization.
An angiogenic role for adrenomedullin in choroidal neovascularization.
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DOI：
10.1371/journal.pone.0058096
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Takakura N
中科院分区：
文献类型：
--
作者：
Sakimoto S;Kidoya H;Kamei M;Naito H;Yamakawa D;Sakaguchi H;Wakabayashi T;Nishida K;Takakura N
肾上腺髓质素（ADM）参与生理和病理性血管生成。本研究的目的是调查是否ADM信号参与脉络膜新生血管（CNV）使用小鼠模型。在8周龄C57 BL/6小鼠中通过激光光凝诱导CNV。ADM mRNA表达在治疗后显著增加，在治疗后4天达到峰值。ADM受体（ADM-R）组分（CRLR、RAMP 2和RAMP 3）在CD 31 + CD 45 −内皮细胞（EC）中的表达高于CD 31 − CD 45 −非EC。炎症刺激不仅在细胞系中而且在脉络膜/视网膜色素上皮复合物的原代培养物中的细胞中上调ADM的表达。TNFα处理的巨噬细胞系的上清液增强了EC的增殖，并且这被ADM拮抗剂ADM部分抑制（22-52）。激光治疗后玻璃体内注射ADM（22-52）或ADM中和单克隆抗体（mAb）与赋形剂治疗的对照相比显著减小CNV的大小（p<0.01）。ADM信号通路参与了激光诱导的CNV的形成，因为ADM拮抗剂和ADM mAb都能显著抑制它。抑制ADM信号通路可能是治疗与年龄相关性黄斑变性相关的CNV的一种有价值的替代治疗方法。
Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45− endothelial cells (ECs) than CD31−CD45− non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22–52). Intravitreous injection of ADM (22–52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration.
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影响因子：
4.4
作者：
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