2024-03-28T16:43:03Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/701312022-11-17T02:08:08Zhdl_2115_20058hdl_2115_149Ecrg4 peptide is the ligand of multiple scavenger receptorsMoriguchi, TetsuoTakeda, ShujiIwashita, ShinzoEnomoto, KeiSawamura, TatsuyaKoshimizu, UichiKondo, Toru490Esophageal 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.Nature Publishing GroupJournal Articleapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/70131https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/70131/2/41598_2018_22440_MOESM1_ESM.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/70131/1/s41598-018-22440-4.pdf2045-2322Scientific reports840482018-03-06enginfo:doi/10.1038/s41598-018-22440-4http://creativecommons.org/licenses/by/4.0/publisher