Wnt5a: A Key Regulator Of Inflammation

Wnt proteins are a family of glycoproteins which upon binding to a member of G-protein coupledreceptor, Frizzled (Fz), activates a scaffolding protein Disheveled (Dvl) to elicit their intracellularsignaling functions. Wnt signaling is classified to canonical (βcatenin-dependent) and noncanonical(βcatenin-independent) pathways. Wnt5a, a member of Wnt proteins, is consistently upregulatedby endotoxin (LPS) and interferon (INF)-γ via Toll-like receptor (TLR) activation.Through up-regulation of inflammatory cytokines including IL-1β, IL-6, IL-8, IL-1α and activation ofinflammatory signaling pathways such as nuclear factor-κB (NF-κB) and JNK, Wnt5a elicitsproinflammatory responses in cells. Over the last decades, Wnt5a has been implicated in a varietyof inflammatory diseases including atherosclerosis, obesity, sepsis, rheumatoid arthritis,psoriasis, melanoma, and tuberculosis. The elevated levels of Wnt5a in inflammatory diseasessupport the hypothesis that this protein could be a prognostic marker of inflammation and itssuppression either through inhibition of upstream signaling pathways or through Wnt signalingantagonists is an attractive target for therapeutic intervention in inflammatory disorders.