CLINICAL IMPLICATIONS OF WNT5A: A MULTIFACETED PLAYER IN CELLULAR SIGNALING AND IMMUNE REGULATION

Abstract

Wnt proteins, a family of highly modified cysteine-rich proteins, play vital roles in embryonic development and tissue homeostasis. This review focuses on Wnt5a, a classical non-canonical Wnt ligand, and its diverse functions in various cellular processes and diseases. Emphasizing its association with the NF-κB pathway, the review explores Wnt5a's impact on immune cells, atherosclerosis, rheumatoid arthritis, psoriasis vulgaris, and sepsis. Wnt5a regulates convergent extension, planar cell polarity, and epithelial-mesenchymal interactions during embryonic development and is implicated in pathological conditions, especially cancer. Its dysregulation is linked to the onset and progression of various diseases. The review details Wnt5a's involvement in signaling cascades and its interaction with receptors, such as ROR1 and 2, Ryk receptor tyrosine kinase, and Frizzled 7-transmembrane receptors. It also discusses Wnt5a expression regulation, emphasizing its upregulation in response to stimuli like pathogens and cytokines, and its role in inducing pro-inflammatory cytokines, linking it to inflammatory disorders' pathogenesis. The review delves into Wnt5a's impact on immune cells, its regulatory effect on dendritic cells, and its influence on macrophage polarization. It addresses Wnt5a's potential as a therapeutic target in inflammatory conditions and cancer. In summary, this comprehensive review provides insights into Wnt5a's multifaceted roles in signaling pathways, immune regulation, and disease pathogenesis, highlighting its potential as a therapeutic target.