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Ecrg4 peptide is the ligand of multiple scavenger receptors
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| Title: | Ecrg4 peptide is the ligand of multiple scavenger receptors |
| Authors: | Moriguchi, Tetsuo Browse this author →KAKEN DB | | Takeda, Shuji Browse this author | | Iwashita, Shinzo Browse this author | | Enomoto, Kei Browse this author | | Sawamura, Tatsuya Browse this author | | Koshimizu, Uichi Browse this author | | Kondo, Toru Browse this author →KAKEN DB |
| Issue Date: | 6-Mar-2018 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Scientific reports |
| Volume: | 8 |
| Start Page: | 4048 |
| Publisher DOI: | 10.1038/s41598-018-22440-4 |
| Abstract: | 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-kappa B 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/70131 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 近藤 亨
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