scholarly journals Wnt Signaling in Vascular Calcification

2021 ◽  
Vol 8 ◽  
Author(s):  
Kaylee Bundy ◽  
Jada Boone ◽  
C. LaShan Simpson
Keyword(s):  
Cardiovascular Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Vascular Calcification ◽  
Arterial Wall ◽  
Wnt Signaling Pathway ◽  
Phenotypic Switch ◽  
Wnt Ligands ◽  
And Function ◽  
Canonical Wnt

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.

Wnt Production in Dental Epithelium Is Crucial for Tooth Differentiation

2019 ◽  
Vol 98 (5) ◽  
pp. 580-588 ◽  
Author(s):  
Y. Xiong ◽  
Y. Fang ◽  
Y. Qian ◽  
Y. Liu ◽  
X. Yang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tooth Development ◽  
Wnt Signaling Pathway ◽  
Conditional Knockout ◽  
Canonical Wnt Signaling ◽  
Odontoblast Differentiation ◽  
Wnt Ligands ◽  
Dental Epithelium ◽  
Canonical Wnt

The Wnt ligands display varied spatiotemporal expression in the epithelium and mesenchyme in the developing tooth. Thus far, the actions of these differentially expressed Wnt ligands on tooth development are not clear. Shh expression specifies the odontogenic epithelium during initiation and is consistently restricted to the dental epithelium during tooth development. In this study, we inactivate Wntless ( Wls), the key regulator for Wnt trafficking, by Shh-Cre to investigate how the Wnt ligands produced in the dental epithelium lineage act on tooth development. We find that conditional knockout of Wls by Shh-Cre leads to defective ameloblast and odontoblast differentiation. WlsShh-Cre teeth display reduced canonical Wnt signaling activity in the inner enamel epithelium and the underlying mesenchyme at the early bell stage, as exhibited by target gene expression and BAT-gal staining. The expression of Wnt5a and Wnt10b is not changed in WlsShh-Cre teeth. By contrast, Wnt10a expression is significantly increased in response to epithelial Wls deficiency. In addition, the expression of Hedgehog signaling pathway components Shh, Gli1, and Patched1 was greatly decreased in WlsShh-Cre teeth. Epithelial Wls loss of function in Shh lineage also leads to aberrant cell proliferation in dental epithelium and mesenchyme at embryonic day 16.5; however, the cell apoptosis is unaffected. Moreover, we find that Decorin and Col1a1, the key markers for odontoblast differentiation that are downregulated in WlsShh-Cre teeth, act as direct downstream targets of the canonical Wnt signaling pathway by chromatin immunoprecipitation analysis. Additionally, Decorin and Col1a1 expression can be increased by lithium chloride (LiCl) treatment in the in vitro tooth explants. Taken together, our results suggest that the spatial expression of Wnt ligands within the dental epithelial lineage regulates the differentiation of tooth structures in later stages.

scholarly journals Wnt Signaling in Red Blood Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4806-4806
Author(s):  
Rina Rosin-Arbesfeld ◽  
Michal Caspi ◽  
Ronen Siman-Tov ◽  
Yakir Levi ◽  
Chava Perry
Keyword(s):  
Life Span ◽  
Wnt Signaling ◽  
Red Blood Cells ◽  
Signaling Pathway ◽  
Blood Cells ◽  
Wnt Signaling Pathway ◽  
Signaling Cascades ◽  
Canonical Wnt Signaling ◽  
Wnt Ligands ◽  
Canonical Wnt

Abstract Introduction : Red blood cells (RBCs) are the most common cell type in the human body. These cells deliver oxygen to the body's tissues and are composed of a cytoplasm that is rich in hemoglobin and is surrounded by a membrane that is essential for the cells function by providing properties such as stability and deformability. The membrane is composed of a lipid bilayer, transmembrane proteins, and a filamentous meshwork of proteins such as actin and adducin that forms the cells cytoskeleton along the entire cytoplasmic surface of the membrane. RBCs lack a nucleus and other cellular organelles that enable gene expression. Thus, it has been assumed, that signaling cascades such as the Wnt signaling pathway are not active in RBCs. The Wnt pathways are fundamental for normal development and homeostasis and regulate, among other, cell growth, motility and differentiation. Although there is no functional data connecting between Wnt signaling and RBCs, previous proteomic studies have shown that some of the non-canonical Wnt signaling components, such as specific small GTPases and kinases are present in RBCs. In this study, we show for the first time that Wnt ligands activate signaling cascades in RBCs. Methods : RBCs were collect from healthy donors and treated with different Wnt ligands. A large number of methods were used to evaluate the RBCs morphological properties, life span, vitality, flexibility and protein expression patterns. Results : Our results clearly show that different Wnt ligands can dramatically increase the live span of RBCs by affecting the cells membrane cytoskeleton. Some of the Wnts affects include activation of GTPases such as Rac, JNK and RhoA, which lead to actin modification. These changes in the actin cytoskeleton result in increased membrane stability. In parallel, treating RBCs with Wnts leads to activation of PKC and RhoA resulting in phosphorylation of adducin which in turn increases the cells membrane flexibility and improves the vitality of the cell. Summary : Our novel findings indicate that the non-canonical Wnt signaling pathway in RBCs is active and can stabilize the RBCs cytoskeleton enhancing the vitality, deformability and life span of the cell. These novel findings may help in the development of new therapeutic strategies for people suffering from different hemolytic disease that effect the RBCs cytoskeleton and provide new insights into the improvement of stored RBC units. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Regulation of Bone Metabolism and Disorders by Wnt Signaling

2019 ◽  
Vol 20 (22) ◽  
pp. 5525 ◽  
Author(s):  
Kazuhiro Maeda ◽  
Yasuhiro Kobayashi ◽  
Masanori Koide ◽  
Shunsuke Uehara ◽  
Masanori Okamoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Wnt Signaling ◽  
Bone Metabolism ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Osteoporosis Treatment ◽  
Biological Phenomena ◽  
Approximate Molecular Weight ◽  
Skeletal Disorders ◽  
Canonical Wnt

Wnt, a secreted glycoprotein, has an approximate molecular weight of 40 kDa, and it is a cytokine involved in various biological phenomena including ontogeny, morphogenesis, carcinogenesis, and maintenance of stem cells. The Wnt signaling pathway can be classified into two main pathways: canonical and non-canonical. Of these, the canonical Wnt signaling pathway promotes osteogenesis. Sclerostin produced by osteocytes is an inhibitor of this pathway, thereby inhibiting osteogenesis. Recently, osteoporosis treatment using an anti-sclerostin therapy has been introduced. In this review, the basics of Wnt signaling, its role in bone metabolism and its involvement in skeletal disorders have been covered. Furthermore, the clinical significance and future scopes of Wnt signaling in osteoporosis, osteoarthritis, rheumatoid arthritis and neoplasia are discussed.

AB0070 Wnt and wisp1 expression in the synovium induces cartilage damage by skewing of tgf-beta signaling via the canonical wnt signaling pathway

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A807.1-A807
Author(s):  
M. H. van den Bosch ◽  
A. B. Blom ◽  
P. L. van Lent ◽  
H. M. van Beuningen ◽  
F. A. van de Loo ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cartilage Damage ◽  
Wnt Signaling Pathway ◽  
Tgf Beta ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1331
Author(s):  
Yung-Fu Wu ◽  
Chih-Yang Wang ◽  
Wan-Chun Tang ◽  
Yu-Cheng Lee ◽  
Hoang Dang Khoa Ta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Mrna Levels ◽  
Key Factor ◽  
Canonical Wnt ◽  
Upregulated Genes

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

Sign in / Sign up

Export Citation Format

Share Document