Ecrg4 peptide is the ligand of multiple scavenger receptors.
Ecrg4 peptide is the ligand of multiple scavenger receptors.
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DOI：
10.1038/s41598-018-22440-4
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发表时间：
2018-03-06
影响因子：
4.6
通讯作者：
Kondo T
中科院分区：
文献类型：
--
作者：
Moriguchi T;Takeda S;Iwashita S;Enomoto K;Sawamura T;Koshimizu U;Kondo T
食道癌相关基因4(Ecrg4)编码一种激素样肽，被认为参与了包括肿瘤抑制在内的多种生理现象。最近对Ecrg4的研究进展表明，Ecrg4是一种促炎因子，可诱导巨噬细胞/小胶质细胞表达多种细胞因子和趋化因子。然而，Ecrg4信号的详细分子机制，特别是Ecrg4受体，仍然知之甚少。在这里，我们利用逆转录病毒介导的表达克隆，鉴定了凝集素样氧化型低密度脂蛋白受体-1(LOX-1)是一个结合Ecrg4(71-132)氨基酸残基(Ecrg4(71-132))的膜蛋白。此外，除了LOX-1，几种清道夫受体，如Scarf1，CD36和Stablin-1，促进了Ecrg4(71-132)有效地内化到细胞内。一种广泛的清道夫受体竞争性抑制剂，多肌苷酸，既减少了小胶质细胞中Ecrg4的结合，也减少了NF-κB的激活。这种激活依赖于MyD88，这是一种适配器蛋白，它将信号蛋白招募到Toll样受体(TLRs)，从而诱导各种免疫反应。这些数据表明，多个清道夫受体识别Ecrg4(71-132)，并在小胶质细胞中与TLRs一起转导Ecrg4信号。
Esophageal cancer-related gene 4 (Ecrg4) encodes a hormone-like peptide that is believed to be involved in a variety of physiological phenomena, including tumour suppression. Recent progress in the study of Ecrg4 has shown that Ecrg4 is a proinflammatory factor and induces the expression of several cytokines and chemokines in macrophages/microglia. However, the detailed molecular mechanisms of Ecrg4 signalling, especially the Ecrg4 receptors, remain poorly understood. Here, using retrovirus-mediated expression cloning, we identified lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) as a membrane protein that binds amino acid residues 71–132 of Ecrg4 (Ecrg4(71–132)). Moreover, in addition to LOX-1, several scavenger receptors, such as Scarf1, Cd36 and Stabilin-1, facilitated the efficient internalisation of Ecrg4(71–132) into cells. A broad competitive inhibitor of scavenger receptors, polyinosinic acid, reduced both the binding of Ecrg4(71–132) and the activation of NF-κB in microglia. This activation was dependent on MyD88, an adaptor protein that recruits signalling proteins to Toll-like receptors (TLRs), with the consequent induction of various immune responses. These data suggest that multiple scavenger receptors recognise Ecrg4(71–132) and transduce its signals, together with TLRs, in microglia.
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影响因子：
9.3
作者：
Fujita, Yoshiko;Kakino, Akemi;Sawamura, Tatsuya
通讯作者：
Sawamura, Tatsuya
DOI：
10.1161/01.atv.18.10.1541
发表时间：
1998-10-01
影响因子：
8.7
作者：
Moriwaki, H;Kume, N;Kita, T
通讯作者：
Kita, T
影响因子：
3.7
作者：
Kurabi A;Pak K;Dang X;Coimbra R;Eliceiri BP;Ryan AF;Baird A
通讯作者：
Baird A
影响因子：
25.7
作者：
Beauvillain, Celine;Meloni, Francesca;Jeannin, Pascale
通讯作者：
Jeannin, Pascale
影响因子：
8.7
作者：
Li, DY;Mehta, JL
通讯作者：
Mehta, JL