الفهرس 
Wnt SignalingOnly 14 pages are availabe for public view
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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.
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 in dermal papilla cells is regulated by androgen and this regulation plays a pivotal role in androgen’s action on hair growth.
Canonical Wnt signaling is required for the induction of the neural crest, β-catenin is important for normal melanocyte biology and canonical Wnt signaling pathway is activated in melanoma.
Hh pathway-directed Wnt signaling is the most likely cause of nuclear β-catenin accumulation in basal cell carcinoma. Non-canonical Wnt signaling, might also be active in the context of repressed canonical Wnt signaling.
No mutations in key members of the canonical Wnt pathway have been identified in Merkel cell carcinoma, and nuclear accumulation of β-catenin has been shown in a small percentage of Merkel cell carcinoma.
The activity of the Wnt canonical pathway in psoriasis has been controversial. There is increased nuclear β-catenin staining in the suprabasal layer in lesional psoriatic skin whereas in other areas showed only membranous staining in lesional psoriatic skin.
In Psoriatic arthritis changes in Wnt signaling components is not clear, elevated serum DKK- 1 concentrations is seen with patients with psoriatic arthritis.
Wnt signaling is involved in skin pigmentation where DKK1 is found to be responsible for thickened and hypopigmented palmoplantar epidermis and the Wnt/β-catenin signaling pathway seemed to mediate the tobacco smoke extract-induced melanocyte activation.
Wnt signaling is essential at multiple steps during the complex organogenesis of the skin and its appendages and for the regeneration of lost skin and skin appendages during wound healing. Wnt signaling has been implicated in the control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state.
Wnt signaling contains multiple levels of regulation that can be manipulated to modulate the pathway; as Wnt receptors, secreted Wnt antagonists and intracellular mediators. Therefore, researchers have been working to develop drugs that target specific components of Wnt signaling. A few agents have shown promising results and are currently undergoing clinical trials. Other drugs continue to be investigated at the preclinical stages.