Ecrg4 peptide is the ligand of multiple scavenger receptors
| Autor: | Toru Kondo, Tatsuya Sawamura, Shinzo Iwashita, Kei Enomoto, Uichi Koshimizu, Shuji Takeda, Tetsuo Moriguchi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemokine CD36 Genetic Vectors Gene Expression lcsh:Medicine Plasma protein binding Article Cell Line Proinflammatory cytokine Mice 03 medical and health sciences Animals Humans Scavenger receptor lcsh:Science Receptor Receptors Scavenger Multidisciplinary biology Chemistry lcsh:R Signal transducing adaptor protein Endocytosis Neoplasm Proteins Rats Cell biology Retroviridae 030104 developmental biology Myeloid Differentiation Factor 88 biology.protein Cytokines lcsh:Q Microglia Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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