Ecrg4 peptide is the ligand of multiple scavenger receptors.
Sci Rep, 2018/03/06;8(1):4048.
Moriguchi T[1], Takeda S[2], Iwashita S[2], Enomoto K[2], Sawamura T[3], Koshimizu U[2], Kondo T[4]
Affiliations
PMID: 29511297DOI: 10.1038/s41598-018-22440-4
Impact factor: 4.996
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-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.
MeSH terms
Animals; Cell Line; Cytokines; Endocytosis; Gene Expression; Genetic Vectors; Humans; Mice; Microglia; Myeloid Differentiation Factor 88; Neoplasm Proteins; Protein Binding; Rats; Receptors, Scavenger; Retroviridae; Signal Transduction
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