The Role of Wnt Signaling In Dermatology

Abstract

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals from outside of a cell to the inside. Three main Wnt signaling pathways have been defined: the canonical Wnt pathway, the non canonical planar cell polarity pathway, and the non canonical Wnt/calcium pathway. The difference between the categories is that a canonical pathway involves the protein β-catenin while a non canonical pathway operates independently of it. All Wnt signaling pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the protein Dishevelled inside the cell. However, to facilitate Wnt signaling, co-receptors may also be required alongside the interaction between the Wnt protein and Frizzled receptor. Examples include low density lipoprotein receptor-related protein (LRP)-5/6, receptor tyrosine kinase (Ryk), and ROR2. The canonical Wnt pathway leads to regulation of gene transcription, the non canonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell, and the non canonical Wnt/calcium pathway regulates calcium inside the cell. Specific Wnt antagonists include Dickkopf (DKK), Wnt inhibitory factor (WIF), secreted Frizzled-related proteins (SFRP), frizzled-related protein (FRZb), Wise and Sclerostin. All of these constitute inhibitors of Wnt signaling. However, other molecules have been shown to act as activators as well. For example, Norrin and R-Spondin have been shown to activate Wnt signaling. 104 The clinical importance of Wnt pathway has been demonstrated by disruptions of its components that lead to a variety of diseases, including rheumatic diseases, dermatological diseases, type II diabetes, tumor formation, hereditary disorders, fibrosis diseases and others. Skin fibrosis in systemic sclerosis is complex and multi-factorial, and in addition to TGF-β, Wnt ligands are involved. Hair follicle development involves tightly coordinated prototypic ectodermal-mesodermal interaction. Wnt signaling can affect the regulation of hair growth and the structure of the hair shaft. Wnt signaling