Wnt/β-catenin signaling pathway in severe preeclampsia

This study aims to elucidate the mechanisms of Wnt/β-catenin signaling pathway in the development of preeclampsia (PE). The mRNA levels of Wnt1, β-catenin, c-myc and cyclinD1 were determined by real-time PCR in the placentas. Moreover, the expression levels of Wnt1, β-catenin, Dickkopf-1 (DKK1) and glycogen synthase kinase 3β (GSK-3β) proteins were detected by Western blot. Immunohistochemistry was used in placental tissue microarray to localize the expression of Wnt1, β-catenin, DKK1 proteins in the placentas of two groups. Compared with the control placentas, the mRNA levels of Wnt1, β-catenin, c-myc and cyclinD1 were decreased in the severe preeclamptic placentas. The Western blot results showed that the expression levels of Wnt1, β-catenin, and GSK-3β proteins were significantly elevated in the control group, while the expression level of DKK1 was significantly decreased. In addition, the staining intensity of Wnt1, β-catenin were weaker in the placentas of the severe PE group while the staining intensity of DKK1 was significantly stronger in the placentas of the severe PE group. Wnt/β-catenin signaling pathway may play a significant role in the pathogenesis of PE by regulating the invasion and proliferation of trophoblast.     

Distinctive microRNA signature associated of neoplasms with the Wnt/β-catenin signaling pathway

As the crucial biological regulators, microRNAs that act by suppressing their target genes are involved in a variety of pathophysiological processes. It is generally accepted that microRNAs are often dysregulated in many types of neoplasm and other human diseases. In neoplasm, microRNAs may function as oncogenes or tumor suppressors. As constitutive activation of the Wnt signaling pathway is a common feature of neoplasm and contributes to its development, progression and metastasis in various cancers, numerous studies have revealed that microRNA-mediated gene regulation are interconnected with the Wnt/β-catenin signaling pathway, forming a Wnt/β-catenin–microRNA regulatory network, which is critical to successful targeting of the Wnt/β-catenin pathway for oncotherapy. In this review, we aim to accumulate recent advances on microRNAs that work in tandem with Wnt/β-catenin signaling in tumorigenesis, with particular focus on how microRNAs affect Wnt/β-catenin activity as well as how microRNAs are regulated through the Wnt/β-catenin pathway.     

Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish

Normal heart formation requires reiterative phases of canonical Wnt/β-catenin (Wnt) signaling. Understanding the mechanisms by which Wnt signaling directs cardiomyocyte (CM) formation in vivo is critical to being able to precisely direct differentiated CMs from stem cells in vitro. Here, we investigate the roles of Wnt signaling in zebrafish CM formation using heat-shock inducible transgenes that increase and decrease Wnt signaling. We find that there are three phases during which CM formation is sensitive to modulation of Wnt signaling through the first 24 h of development. In addition to the previously recognized roles for Wnt signaling during mesoderm specification and in the pre-cardiac mesoderm, we find a previously unrecognized role during CM differentiation where Wnt signaling is necessary and sufficient to promote the differentiation of additional atrial cells. We also extend the previous studies of the roles of Wnt signaling during mesoderm specification and in pre-cardiac mesoderm. Importantly, in pre-cardiac mesoderm we define a new mechanism where Wnt signaling is sufficient to prevent CM differentiation, in contrast to a proposed role in inhibiting cardiac progenitor (CP) specification. The inability of the CPs to differentiate appears to lead to cell death through a p53/Caspase-3 independent mechanism. Together with a report for an even later role for Wnt signaling in restricting proliferation of differentiated ventricular CMs, our results indicate that during the first 3days of development in zebrafish there are four distinct phases during which CMs are sensitive to Wnt signaling.     

Wnt/β-catenin signaling and disease

The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future.     

LINC00365 promotes colorectal cancer cell progression through the Wnt/β-catenin signaling pathway

In the past decade, substantial evidence established that long noncoding RNAs are serious about mediating the evolution of malignancies. In previous studies, LINC00365, which has not been reported in colorectal cancer (CRC), was selected using the bioinformatics analysis in GSE109454 and GSE41655 data sets. However, the function and mechanism of LINC00365 are still obscure. In our study, LINC00365 was found upregulated in CRC specimens and intimately connected with the prognosis of patients with CRC. In addition, LINC00365 overexpression enhances the cell abilities of proliferation, migration, and invasion in vitro. Meanwhile, mechanistic studies showed that LINC00365 might involve in CRC cell progression by mediating the Wnt/β-catenin pathway. Furthermore, LINC00365 upregulation increased CDK1 protein expression. In conclusion, this study suggests that LINC00365 acts as a vital part in facilitating CRC progression and might play as a therapeutic target for patients with CRC.     

Ectodermal Wnt/β-catenin signaling shapes the mouse face

The canonical Wnt/β-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional β-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing β-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/β-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution.     

Gene–gene interactions of the Wnt/β-catenin signaling pathway in knee osteoarthritis

Molecular Biology Reports - This study was designed to investigate whether genetic polymorphisms of the Wnt/β-catenin signaling pathway and its interactions are involved in the development of...     

Wnt/β-catenin signaling in hepatic organogenesis

Wnt/β-catenin signaling has come to the forefront of liver biology in recent years. This pathway regulates key pathophysiological events inherent to the liver including development, regeneration, and cancer, by dictating several biological processes such as proliferation, apoptosis, differentiation, adhesion, zonation and metabolism in various cells of the liver. This review will examine the studies that have uncovered the relevant roles of Wnt/β-catenin signaling during the process of liver development. We will discuss the potential roles of Wnt/β-catenin signaling during the phases of development, including competence, hepatic induction, expansion, and morphogenesis. In addition, we will discuss the role of negative and positive regulation of this pathway and how the temporal expression of Wnt/β-catenin can direct key processes during hepatic development. We will also identify some of the major deficits in the current understanding of the role of Wnt/β-catenin signaling in liver development in order to provide a perspective for future studies. Thus, this review will provide a contextual overview of the role of Wnt/β-catenin signaling during hepatic organogenesis.     

Regulation of cadherin expression in the chicken neural crest by the Wnt/β-catenin signaling pathway

In neural crest cell development, the expression of the cell adhesion proteins cadherin-7 and cadherin-11 commences after delamination of the neural crest cells from the neuroepithelium. The canonical Wnt signaling pathway is known to drive this delamination step and is a candidate for inducing expression of these cadherins at this time. This project was initiated to investigate the role of canonical Wnt signaling in the expression of cadherin-7 and cadherin-11 by treating neural crest cells with Wnt3a ligand. Expression of cadherin-11 was first confirmed in the neural crest cells for the chicken embryo. The changes in the expression level of cadherin-7 and -11 following the treatment with Wnt3a were studied using real-time RT-PCR and immunostaining. Statistically significant upregulation in the mRNA expression of cadherin-7 and cadherin-11 and in the amount of cadherin-7 and cadherin-11 protein found in cell-cell interfaces between neural crest cells was observed in response to Wnt, demonstrating that cadherin-7 and cadherin-11 expressed by the migrating neural crest cells can be regulated by the canonical Wnt pathway.Key words: neural crest, Wnt, cadherin-7, cadherin-11     

Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway

Journal of Physiology and Biochemistry - Gastric cancer (GC) is one of the most common cancers, with most patients often succumbing to death as a result of tumor metastasis. Recent work has...     

Functions of the Wnt/β-catenin pathway in an anemia-induced zebrafish model of cardiomyopathy are location dependent

Recent evidence that the heart is not a terminally-differentiated organ has provided more credence to investigations of pathways involved in inducing cardiomyocyte (CM) hyperplasia as a therapy for heart disease. Here, we leveraged zebrafish as a novel vertebrate model of cardiomyopathy to explore the therapeutic potential based on the Wnt/β-catenin signaling. In the anemia-induced zebrafish model of cardiomyopathy (tr265), we detected differently regulated CM hyperplasia and CM hypertrophy in the compact region and the trabecular region. To assess the effects of the Wnt/β-catenin pathway on these two regions, the anemia line was crossed with heat shock-inducible transgenic fish to upregulate or downregulate the pathway. Upregulation resulted in increased cardiomyocyte hyperplasia in the heart and increased cardiomyocyte hypertrophy in the trabecular region, while downregulation resulted in reduced cardiomyocyte hyperplasia in the heart and reduced cardiomyocyte hypertrophy in the trabecular region. Importantly, upregulation of the pathway resulted in improved fish survival, while downregulation decreased it. In summary, our data suggested that (1) the compact region and the trabecular region respond differently during cardiac remodeling; (2) activation of the Wnt/β-catenin pathway might exert a cardioprotective function via promoting cardiomyocyte hyperplasia.     

TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/β-catenin signaling pathway

TRIM29 plays an important role in many neoplasms.In this study,we aimed to elucidate its role in hepatocellular carcinoma (HCC) and explore the corresponding potential mechanism.The expression level of TRIM29 in HCC samples and hepatoma cell lines was detected.We found that TRIM29 was down-regulated in clinical HCC samples and cultured hepatoma cell lines by western blot analysis and quantitative polymerase chain reaction.In addition,we demonstrated that higher TRIM29 expression was associated with higher differentiation grade of HCC.To explore the effect of TRIM29 on hepatoma cells and its possible mechanisms,TRIM29-knockdown and overexpression cell models were constructed.The results showed that the depletion of TRIM29 promoted liver cancer cell proliferation,clone formation,migration and invasion in vitro probably through the Wnt/β-catenin signaling pathway.This study revealed the inhibitory roles of TRIM29 in HCC and the possible mechanisms.     

CTSB promotes porcine preadipocytes differentiation by degrading fibronectin and attenuating the Wnt/β-catenin signaling pathway

The process of preadipocytes differentiation plays a vital role in adipose tissue expansion and many factors are involved in this event. Cathepsin B (CTSB), secreted from lysosome, has been reported in regulating a variety of physiological processes. In this study, we demonstrated CTSB promotes lipid accumulation and adipogenic genes expression in porcine primary preadipocytes by degrading fibronectin (Fn), a key component of extracellular matrix. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling through stabilizing β-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl, indicating that CTSB could impact Wnt/β-catenin signaling pathway. Interestingly, Fn is an important target gene of Wnt/β-catenin. So we considered that CTSB promote preadipocytes differentiation by suppressing these two pathways.