Wnt signaling in biliary development, proliferation, and fibrosis

2021 ◽  
pp. 153537022110613
Author(s):  
Lipeng Tian ◽  
Yichen Wang ◽  
Yoon Young Jang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Embryonic Stem ◽  
Ductular Reaction ◽  
Ductal Cells ◽  
Underlying Mechanisms

Biliary fibrosis is an important pathological indicator of hepatobiliary damage. Cholangiocyte is the key cell type involved in this process. To reveal the pathogenesis of biliary fibrosis, it is essential to understand the normal development as well as the aberrant generation and proliferation of cholangiocytes. Numerous reports suggest that the Wnt signaling pathway is implicated in the physiological and pathological processes of cholangiocyte development and ductular reaction. In this review, we summarize the effects of Wnt pathway in cholangiocyte development from embryonic stem cells, as well as the underlying mechanisms of cholangiocyte responses to adult ductal damage. Wnt signaling pathway is regulated in a step-wise manner during each of the liver differentiation stages from embryonic stem cells to functional mature cholangiocytes. With the modulation of Wnt pathway, cholangiocytes can also be generated from adult liver progenitor cells and mature hepatocytes to repair liver damage. Non-canonical Wnt signaling is triggered in the active ductal cells during biliary fibrosis. Targeted control of the Wnt signaling may hold the great potential to reduce and/or reverse the biliary fibrogenic process.

scholarly journals Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo

2015 ◽  
Vol 13 (1) ◽  
pp. 720-730 ◽  
Author(s):  
LIPING OU ◽  
LIAOQIONG FANG ◽  
HEJING TANG ◽  
HAI QIAO ◽  
XIAOMEI ZHANG ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

Targeting Wnt Signaling through Small molecules in Governing Stem Cell Fate and Diseases

2019 ◽  
Vol 19 (3) ◽  
pp. 233-246 ◽  
Author(s):  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Suhanya Veronica Prasad ◽  
Francesco Marotta ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Small Molecules ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Stem Cell Fate

Background:The conserved Wnt/β-catenin signaling pathway is responsible for multiple functions including regulation of stem cell pluripotency, cell migration, self-renewability and cell fate determination. This signaling pathway is of utmost importance, owing to its ability to fuel tissue repair and regeneration of stem cell activity in diverse organs. The human adult stem cells including hematopoietic cells, intestinal cells, mammary and mesenchymal cells rely on the manifold effects of Wnt pathway. The consequences of any dysfunction or manipulation in the Wnt genes or Wnt pathway components result in specific developmental defects and may even lead to cancer, as it is often implicated in stem cell control. It is absolutely essential to possess a comprehensive understanding of the inhibition and/ or stimulation of the Wnt signaling pathway which in turn is implicated in determining the fate of the stem cells.Results:In recent years, there has been considerable interest in the studies associated with the implementation of small molecule compounds in key areas of stem cell biology including regeneration differentiation, proliferation. In support of this statement, small molecules have unfolded as imperative tools to selectively activate and inhibit specific developmental signaling pathways involving the less complex mechanism of action. These compounds have been reported to modulate the core molecular mechanisms by which the stem cells regenerate and differentiate.Conclusion:This review aims to provide an overview of the prevalent trends in the small molecules based regulation of stem cell fate via targeting the Wnt signaling pathway.

scholarly journals ER71 specifies Flk-1+ hemangiogenic mesoderm by inhibiting cardiac mesoderm and Wnt signaling

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3295-3305 ◽  
Author(s):  
Fang Liu ◽  
Inyoung Kang ◽  
Changwon Park ◽  
Li-Wei Chang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cell ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Wnt Signaling Pathway ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Mesoderm Specification ◽  
In The Wild ◽  
Ets Transcription Factor

Abstract Two distinct types of Flk-1+ mesoderm, hemangiogenic and cardiogenic, are thought to contribute to blood, vessel, and cardiac cell lineages. However, our understanding of how Flk-1+ mesoderm is specified is currently limited. In the present study, we investigated whether ER71, an Ets transcription factor essential for hematopoietic and endothelial cell lineage development, could modulate the hemangiogenic or cardiogenic outcome of the Flk-1+ mesoderm. We show that Flk-1+ mesoderm can be divided into Flk-1+PDGFRα− hemangiogenic and Flk-1+PDGFRα+ cardiogenic mesoderm. ER71-deficient embryonic stem cells produced only the Flk-1+PDGFRα+ cardiogenic mesoderm, which generated SMCs and cardiomyocytes. Enforced ER71 expression in the wild-type embryonic stem cells skewed toward the Flk-1+PDGFRα− mesoderm formation, which generated hematopoietic and endothelial cells. Whereas hematopoietic and endothelial cell genes were positively regulated by ER71, cardiac and Wnt signaling pathway genes were negatively regulated by ER71. We show that ER71 could inhibit Wnt signaling in VE-cadherin–independent as well as VE-cadherin–dependent VE-cadherin/β-catenin/Flk-1 complex formation. Enforced β-catenin could rescue cardiogenic mesoderm in the context of ER71 overexpression. In contrast, ER71-deficient Flk-1+ mesoderm displayed enhanced Wnt signaling, which was reduced by ER71 re-introduction. We provide the molecular basis for the antagonistic relationship between hemangiogenic and cardiogenic mesoderm specification by ER71 and Wnt signaling.

scholarly journals Mechanism of Wnt Pathway on Cartilage Differentiation of Adipose-Derived Stem cells

2020 ◽  
Author(s):  
Wanwu Dai ◽  
Bo Zhang ◽  
Zuquan Huang ◽  
Guili Sun ◽  
Yejing Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Chondrogenic Differentiation ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Adipose Derived Stem Cells ◽  
Expression Levels ◽  
Cartilage Differentiation ◽  
Late Stages

Abstract Background: Adipose-derived stem cells ( ADSCs ) therapy is considered as a promising alternative to treat osteoarthritis (OA).Considerable evidence has shown that the Wnt signaling pathway is involved in chondrogenic differentiation in various stem cells.In the present study, we explored in detail the mechanism of of Wnt signaling pathway in the regulation of adipose-derived stem cell chondrogenic differentiation.Methohs: Adipose-derived stem cells were extracted from Sprague-Dawley groin area, isolated, cultured and verified. Then LiCl and DKK-1 used to induce ADSCs cartilage differentiation to detect indicators of cartilage at different stages, such as collagen type II (Collagen2a), aggrecan (Aggrecan) and Wnt pathway key proteins Sox9, β-catenin, Glycogen synthase kinase-3β (GSK-3β) expression.Subsequently, lentivirus was used as the vector, the full-length Sox9 gene was transfected into ADSCs and the expression levels of relevant indicators were detected again after stable expression.Results: In the process of inducing differentiation, the Wnt pathway promoted the rapid proliferation of ADSCs in the early, middle and late stages, and up-regulates Sox9 expression.Cartilage indicators Collagen 2a and Aggrecan expression levels were not significantly increased in the early stage, but significantly increased in the middle and late stages (P <0.05). At the later stage, however, the Wnt pathway down-regulated Sox9 expression, weakened the mature cartilage phenotype, promoted cartilage hypertrophy and early cartilage ossification. Finally, the overexpression of Sox9 feedback inhibits the Wnt pathway activity, down-regulates β-catenin expression, maintains cartilage phenotype, delays cartilage hypertrophy and early osteogenesis.Conclusion:The Wnt pathway regulates chondrogenic differentiation of ADSCs by regulating Sox9, but its regulatory mechanism is significantly different at different stages of induced differentiation.

Sign in / Sign up

Export Citation Format

Share Document