Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

Abstract

The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases.

Paediatric‐onset and adult‐onset Graves' disease share multiple genetic risk factors

“…41 Dysregulation of the Wnt/beta-catenin signalling pathway may alternate regulatory T cell function and it has been suggested as a potential novel therapeutic target in autoimmune disorders. 42 Interestingly, PRICKLE1 has been identified as a GD risk locus in the Immunochip study, 32 and we showed that the PRICKLE1 risk variant was nominally more frequent in POGD comparing to AOGD patients in our study and it might be associated with age of GD onset.…”

“…While initially associated with planar cell polarity, the PRICKLE1 gene encodes a nuclear receptor acting as a negative regulator of the Wnt/beta‐catenin signalling pathway, which, among others, plays also a crucial role in T cell development and differentiation . Dysregulation of the Wnt/beta‐catenin signalling pathway may alternate regulatory T cell function and it has been suggested as a potential novel therapeutic target in autoimmune disorders . Interestingly, PRICKLE1 has been identified as a GD risk locus in the Immunochip study, and we showed that the PRICKLE1 risk variant was nominally more frequent in POGD comparing to AOGD patients in our study and it might be associated with age of GD onset.…”

The roles of signaling pathways in bone repair and regeneration

“…Wnt proteins are members of a family secreted molecules, which bind to their seven-pass transmembrane Frizzled (FZD) receptors and result in the activation of the central player of the pathway, β-catenin at downstream (Gruber, Yee, & Tolwinski, 2016). This signaling plays a substantial function in cell proliferation, differentiation, growth, survival, development, regeneration, self-renewal, and cell fate determination (Shi et al, 2016). Because It regulates a broad range of the cell-fate decisions related to osteogenesis, Wnt signaling has been suggested to be involved throughout the healing process (Krishnan, Bryant, & MacDougald, 2006).…”

The Role of Signaling Pathway on Osteoprogenitor Cell Behavior and Bone Formation

“…Wnt, as a large family of ligands, for membranespooning frizzled (FZD) receptors, is involved in proliferation, growth, migration, polarity, differentiation, and cell death (40,41 …”