The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators

The Wnt signaling pathway regulates physiological processes such as cell proliferation and differentiation, cell fate decisions, and stem cell maintenance and, thus, plays essential roles in embryonic development, but also in adult tissue homeostasis and repair. The Wnt signaling pathway has been associated with heart development and repair and has been shown to be crucially involved in proliferation and differentiation of progenitor cells into cardiomyocytes. The investigation of the role of the Wnt signaling pathway and the regulation of its expression/activity in atrial fibrillation has only just begun. The present minireview (I) provides original data regarding the expression of Wnt signaling components in atrial tissue of patients with atrial fibrillation or sinus rhythm and (II) summarizes the current state of knowledge of the regulation of Wnt signaling components’ expression/activity and the contribution of the various levels of the Wnt signal transduction pathway to the processes of the development, maintenance, and progression of atrial fibrillation.

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

Journal of Immunology Research ◽

10.1155/2016/9392132 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 44

Author(s):

Juan Shi ◽

Shuhong Chi ◽

Jing Xue ◽

Jiali Yang ◽

Feng Li ◽

...

Keyword(s):

Autoimmune Diseases ◽

Wnt Signaling ◽

Signaling Pathway ◽

Noncoding Rna ◽

Cellular Proliferation ◽

Wnt Signaling Pathway ◽

Autoimmune Disorders ◽

Therapeutic Interventions ◽

Curative Therapy ◽

Small Noncoding Rna

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.

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Wnt Signaling in Inflammation in Tissue Repair and Regeneration

Current Protein and Peptide Science ◽

10.2174/1389203720666190507094441 ◽

2019 ◽

Vol 20 (8) ◽

pp. 829-843 ◽

Cited By ~ 1

Author(s):

Yang Zhou ◽

Joy Jin ◽

Mei Feng ◽

Di Zhu

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Immune Cells ◽

Tissue Repair ◽

Wnt Signaling Pathway ◽

The Body ◽

Tissue Repair And Regeneration ◽

Cell Proliferation And Differentiation ◽

First Response ◽

Proliferation And Differentiation

Inflammation is the first response occurring after damage or infection, which is a defensive process for the body. It is well known that excessive inflammation can lead to further diseases such as fibrosis. But a regenerative inflammatory response can accelerate the process of repairing injury, in which a variety of cytokines, immune cells, and stem cells are involved. The Wnt signaling pathway was originally known in the field of development. Recently, its role in regenerative inflammation has gradually been established. Wnt signaling can regulate cell proliferation and differentiation through regulating participants of regenerative inflammation. Canonical and noncanonical Wnt signaling pathways are coordinated to maintain homeostasis. Based on the process of regenerative inflammation and recent research in this field, this paper reviews how the Wnt signaling pathway interact with other cells and pathways.

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Oligodendrocytes Development and Wnt Signaling Pathway

International Journal of Human Anatomy ◽

10.14302/issn.2577-2279.ijha-18-2407 ◽

2018 ◽

Vol 1 (3) ◽

pp. 17-35 ◽

Cited By ~ 2

Author(s):

Shahid Hussain Soomro ◽

Jifu Jie ◽

Hui Fu

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Developmental Stages ◽

Critical Role ◽

Wnt Signaling Pathway ◽

Study Groups ◽

Multiple Roles ◽

Proliferation And Differentiation ◽

Early Developmental

Oligodendrocytes are specialized glial cell in central nervous system (CNS) responsible for the formation of myelin sheath around the axon. Oligodendrocyte proliferation and differentiation is regulated by Wnt signaling pathway, at various stages. However, different study groups have described controversial conclusions about the effect of Wnt on oligodendrocytes precursor cells (OPCs) development. Initially it has been proposed that Wnt pathway negatively regulates the OPCs proliferation and differentiation but recently some studies have described that Wnt promotes the differentiation of OPCs. After carefully reviewing the literature, we believe that Wnt play multiple roles in OPCs differentiation and its function is time (stage) and dose sensitive. Low to moderate activation of Wnt promotes OPC development, while too much or too low is inhibitory. Current evidences also suggested that in early developmental stages, Wnt inhibits the OPCs formation from neural progenitors and differentiation into immature oligodendrocytes. But in late stages Wnt plays promoting role in differentiation and maturation of oligodendrocytes. This review summarized the updated information regarding the critical role of Wnt signaling cascade in proliferation and differentiation of OPCs.

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The Role of Wnt and R-spondin in the Stomach During Health and Disease

Biomedicines ◽

10.3390/biomedicines7020044 ◽

2019 ◽

Vol 7 (2) ◽

pp. 44 ◽

Cited By ~ 3

Author(s):

Anne-Sophie Fischer ◽

Michael Sigal

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Regulatory Function ◽

Healthy State ◽

Organ Systems ◽

Proliferation And Differentiation ◽

Health And Disease ◽

H Pylori

The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, proliferation and differentiation. Deregulation of Wnt signaling is involved in various pathological conditions and has been linked to malignant tissue transformation in different organ systems. The study of the Wnt signaling pathway has revealed a complex regulatory network that tightly balances the quality and strength of Wnt signaling in tissues. In this context, R-spondins are secreted proteins that stabilize Wnt receptors and enhance Wnt signaling. In this review we focus on new insights into the regulatory function of Wnt and R-spondin signaling in the stomach. In addition to its function in the healthy state, we highlight the connection between Wnt signaling and infection with Helicobacter pylori (H. pylori), a pathogen that colonizes the stomach and is the main risk factor for gastric cancer. In addition to experimental data that link Wnt signaling to carcinogenesis, we discuss that Wnt signaling is affected in a substantial proportion of patients with gastric cancer, and provide examples for potential clinical implications for altered Wnt signaling in gastric cancer.

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Conditional Deletion of Foxg1 Alleviates Demyelination and Facilitates Remyelination via the Wnt Signaling Pathway in Cuprizone-Induced Demyelinated Mice

Neuroscience Bulletin ◽

10.1007/s12264-020-00583-7 ◽

2020 ◽

Author(s):

Fuxing Dong ◽

Dajin Liu ◽

Feiyu Jiang ◽

Yaping Liu ◽

Xiuxiang Wu ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Critical Role ◽

Wnt Signaling Pathway ◽

Conditional Knockout ◽

Demyelinating Diseases ◽

Vital Event ◽

Proliferation And Differentiation ◽

Gsk 3Β

Abstract The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

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