WNT7a

Wnt signaling plays an important role in adult brain function, and its dysregulation has been implicated in the loss of neuronal homeostasis. Despite the existence of many studies on the participation of the Wnt pathway in adult neurons, its regulation in astrocytes has been scarcely explored. Several reports point to the presence of Wnt ligands in astrocytes and their possible impact on neuronal plasticity or neuronal death. We aimed to analyze the effect of the neurotransmitter glutamate and the inflammatory cytokine TNFα on the mRNA and protein levels of the canonical Wnt agonist Wnt7a and the antagonist Dkk1 in cultured astrocytes...

Vertebrate organs require locally adapted blood vessels1,2 . The gain of such organotypic vessel specializations is often deemed to be molecularly unrelated to the process of organ vascularization. Here, opposing this model, we reveal a molecular mechanism for brain-specific angiogenesis that operates under the control of Wnt7a/b ligands-well-known blood-brain barrier maturation signals3-5 . The control mechanism relies on Wnt7a/b-dependent expression of Mmp25, which we find is enriched in brain endothelial cells...

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC)...

We have recently made the strikingly discovery that upon a muscle injury, Wnt7a is upregulated and secreted from new regenerating myofibers on the surface of exosomes to elicit its myogenerative response distally. Despite recent advances in extracellular vesicle (EVs) isolation from diverse tissues, there is still a lack of specific methodology to purify EVs from muscle tissue. To eliminate contamination with non-EV secreted proteins and cytoplasmic fragments, which are typically found when using classical methodology, such as ultracentrifugation, we adapted a protocol combining Tangential Flow Filtration (TFF) and Size Exclusion Chromatography (SEC)...

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair...

Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in mdx muscle, a model for Duchenne muscular dystrophy (DMD). However, loss-of-function studies to investigate the requirement for Wnt7a in muscle regeneration has not been evaluated. Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was specifically deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver...

INTRODUCTION: Wnt-signaling is a key regulator of stem cell homeostasis, extensively studied in the intestinal crypt and other metazoan tissues. Yet, there is hardly any data available on the presence of Wnt-signaling components in the adult enteric nervous system (ENS) in vivo . METHODS: Therefore, we employed RNAscope HiPlex-assay, a novel and more sensitive in situ hybridization technology. By amplifying target specific signals, this technique enables the detection of low abundance, tightly regulated RNA content as is the case for Wnt-signaling components...

Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction and inflammation following mild respiratory SARS-CoV-2 infection. To this end, we conduced unbiased transcriptional analysis to identify brain endothelial cell signaling pathways dysregulated by mouse adapted SARS-CoV-2 MA10 in aged immunocompetent C57Bl/6 mice in vivo. This analysis revealed significant suppression of Wnt/β-catenin signaling, a critical regulator of blood-brain barrier (BBB) integrity...

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry...

BACKGROUND: The triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer with high aggressiveness. Although paclitaxel-based chemotherapy scenario present the mainstay in TNBC treatment, paclitaxel resistance is still a striking obstacle for cancer cure. So it is imperative to probe new therapeutic targets through illustrating the mechanisms underlying paclitaxel chemoresistance. METHODS: The Single cell RNA sequencing (scRNA-seq) data of TNBC cells treated with paclitaxel at different points were downloaded from the Gene Expression Omnibus (GEO) database...

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain...

Background: Pancreatic adenocarcinoma (PAAD) is a frequent digestive system cancer, which has high mortality and bad outcome. However, the role of basement membrane (BM)-related gene in assessing patient's outcome, microenvironment and treatment response remain unclear. Methods: Basement membrane (BM)-associated genes were detected by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses using data from the TCGA databases. A risk score system was constructed to distinguish patients in the high- and low-risk groups...

The blood-brain barrier consists of tightly connected endothelial cells protecting the brain's microenvironment from the periphery. These endothelial cells are characterized by specific tight junction proteins such as Claudin-5 and Occludin, forming the endothelial barrier. Disrupting these cells might lead to blood-brain barrier dysfunction. The Wnt/β-catenin signaling pathway can regulate the expression of these tight junction proteins and subsequent barrier permeability. The aim of this study was to investigate the in vitro effects of Wnt7a mediated β-catenin signaling on endothelial barrier integrity...

BACKGROUND: Endometriosis (EM) greatly affects women's reproductive health, identifying new drug targets for EM is urgently needed. This study utilizes comprehensive genome-wide Mendelian randomization (MR) and colocalization analyses, using genomic data, to identify potential therapeutic approaches for EM. METHODS: Genome-wide cis-expression quantitative trait loci (cis-eQTL) data were obtained from GTEx V8, which included 838 participants across 49 tissues or cells, and the eQTLGen consortium, which included 31,684 participants...

The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineer endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways...

The role of 5-methylcytosine (m5C) in tumor initiation and progression has been increasingly recognized. However, the precise association between the regulation of m5C and the progression, metastasis, and prognosis of head and neck squamous cell carcinoma (HNSCC) has not yet been fully explored. Data from 545 HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database were analyzed. Unsupervised cluster analysis was conducted using the expression levels of m5C regulatory genes. Additionally, gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), and Cox regression analysis were utilized...

Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis...

As the human thymus ages, it undergoes a transformation into adipose tissue known as TAT. Interestingly, in previous research, we observed elevated levels of vascular endothelial growth factor A (VEGFA) in TAT from patients with ischemic cardiomyopathy (IC), particularly in those over 70 years old. Moreover, in contrast to subcutaneous adipose tissue (SAT), TAT in elderly individuals exhibits enhanced angiogenic properties and the ability to stimulate tube formation. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery...

Adhesion of the implanting blastocyst involves the interaction between integrin proteins expressed by trophoblast cells and components present in the basement membrane of the endometrial luminal epithelium. Although several factors regulating integrins and their adhesion to fibronectin are already known, we showed that Wnt signaling is involved in the regulation of blastocyst adhesion through the trafficking of integrins expressed by trophoblast cells. Localization of Itgα5β1 by immunofluorescence and FN-binding assays were conducted on peri-implantation blastocysts treated with either Wnt5a or Wnt7a proteins...

OBJECTIVES: Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells...