scholarly journals MCC Regulator of WNT Signaling Pathway (MCC) Is a Podocyte Essential Gene

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Song ◽  
Lulu Zhuang ◽  
Xiaodong Xu ◽  
Jingsong Shi ◽  
Weixin Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Essential Gene ◽  
Wnt Signaling Pathway ◽  
Essential Genes ◽  
Actin Stress Fiber ◽  
Gene Encoding ◽  
Filtration Barrier ◽  
And Function

Podocytes are an integral part of the glomerular filtration barrier. Many genes are already known to be essential for podocyte survival, structure and function, but there are more podocyte essential genes to be identified. By single-cell RNA-seq of mouse podocytes, we detected the expression of gene encoding MCC regulator of WNT signaling pathway (MCC) in majority of the podocytes and speculated that MCC is essential for podocytes. We confirmed MCC expression in mouse podocytes and further showed its expression in human podocytes. To experimentally prove the essentiality of MCC for podocytes, we knocked down MCC in cultured podocytes and found marked morphological change of cell shape, cytoskeletal F-actin stress fiber disruption, increased apoptosis, and downregulation of podocyte essential genes, CD2AP and WT1, demonstrating that MCC is essential for podocytes. Since MCC has been implicated in cell cycle and β-catenin signaling, we examined the expression of cell cycle related genes and activity of β-catenin in the MCC knockdown podocytes, but did not find significant changes. To further explore the mechanism underlying the role of MCC in podocytes, we performed RNA-sequencing and bioinformatics analysis of MCC knockdown podocytes and found a significant enrichment of the regulated genes in lamellipodia formation. Consistently, we found that MCC is present in lamellipodia and MCC knockdown resulted in loss of lamellipodia in the cells. Lastly, we found that MCC was downregulated in podocytes treated with puromycin aminonucleosides and in glomeruli of diabetic mice and FSGS patients, implicating MCC is involved in the development of podocytopathy and proteinuria. In conclusion, MCC is potentially essential for podocytes and its downregulation may be involved in podocytopathy.

S1271 Plantago Ovata Husk Regulates Cell Cycle Progression and Wnt Signaling Pathway, Crucial Elements Implicated in Colorectal Carcinogenesis

2009 ◽  
Vol 136 (5) ◽  
pp. A-226
Author(s):  
Vanessa R. Sapoznik ◽  
Michael N. Grzybowski ◽  
Rosa M. Xicola ◽  
Brian J. Doyle ◽  
Jessica Grzybowski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Wnt Signaling Pathway ◽  
Colorectal Carcinogenesis ◽  
Plantago Ovata ◽  
Cycle Progression

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.

Combination of Salinomycin and AZD3463 Reveals Synergistic Effect on Reducing the Viability of T98G Glioblastoma Cells

2020 ◽  
Vol 20 (18) ◽  
pp. 2267-2273 ◽  
Author(s):  
Aycan Asik ◽  
Neslihan P.O. Ay ◽  
Bakiye G. Bagca ◽  
Hasan O. Caglar ◽  
Cumhur Gunduz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synergistic Effect ◽  
Wnt Signaling ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Combination Treatment ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Expression Levels ◽  
Induced Apoptosis

Background: Salinomycin, an ionophore antibiotic, is known to be an effective agent in reducing the viability of Glioblastoma (GBM) cells. The combination of salinomycin with other chemotherapeutic drugs would help to overcome the drug resistance of GBM cells. Objective: This study aims to test the combinatorial effect of salinomycin and AZD3463 in T98G GBM cells. Methods: The cytotoxic effects of drugs on T98G GBM cells were determined by using WST-8 assay. Flow cytometry was used to identify apoptosis and cell cycle profiles after treatments. Real-time PCR was used to portray mRNA expression profiles of genes in the Wnt-signaling pathway after treatments. Results: IC50 concentrations of AZD3463 and salinomycin were 529nM and 7.3μM for 48h, respectively. The combination concentrations of AZD3463 and salinomycin were 3.3μM and 333nM, respectively. The combination treatment showed a synergistic effect on reducing the viability of GBM cells. AZD3463, salinomycin, and their combination induced apoptosis in 1.2, 1.4, and 3.2 folds, respectively. AZD3463 and the combination treatment induced the cell cycle arrest at the G1 phase. Salinomycin and AZD3463 treatments, either alone or in combination, resulted in the downregulation or upregulation of mRNA expression levels of genes in the Wntsignaling pathway. Conclusion: Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in GBM cells due to a decrease in expression levels of genes acting in both the canonical and non-canonical Wnt signaling pathways. The Wnt signaling pathway may be involved in salinomycin-AZD3463 drug interaction.

scholarly journals MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769502 ◽  
Author(s):  
Taiwei Jiao ◽  
Yue Li ◽  
Tong Gao ◽  
Yining Zhang ◽  
Mingliang Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Wnt Signaling Pathway ◽  
Lovo Cell ◽  
Induced Apoptosis ◽  
Cancer Tissues

MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.

scholarly journals Physalis peruviana-Derived 4β-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1146 ◽  
Author(s):  
Zhen-Nan Ye ◽  
Feng Yuan ◽  
Jie-Qing Liu ◽  
Xing-Rong Peng ◽  
Tao An ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Physalis Peruviana

Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/β-catenin signaling pathway. Physalis peruviana-derived 4βHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 μΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4βHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4βHWE promoted the phosphorylation and degradation of β-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4βHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4βHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4βHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/β-catenin signaling pathway. In conclusion, our study suggested that 4βHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.

scholarly journals 1,25-Vitamin D3 promotes cardiac differentiation through modulation of the WNT signaling pathway

2014 ◽  
Vol 53 (3) ◽  
pp. 303-317 ◽  
Author(s):  
Su M Hlaing ◽  
Leah A Garcia ◽  
Jaime R Contreras ◽  
Keith C Norris ◽  
Monica G Ferrini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vitamin D ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Heart Development ◽  
Wnt Signaling Pathway ◽  
Cardiac Differentiation ◽  
Cell Renewal ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low levels of vitamin D are associated with high risk of myocardial infarction, even after controlling for factors associated with coronary artery disease. A growing body of evidence indicates that vitamin D plays an important role in CVD-related signaling pathways. However, little is known about the molecular mechanism by which vitamin D modulates heart development. The WNT signaling pathway plays a pivotal role in tissue development by controlling stem cell renewal, lineage selection and, even more importantly, heart development. In this study, we examined the role of 1,25-D3(the active form of vitamin D) on cardiomyocyte proliferation, apoptosis, cell phenotype, cell cycle progression and differentiation into cardiomyotubes. We determined that the addition of 1,25-D3to cardiomyocytes cells: i) inhibits cell proliferation without promoting apoptosis; ii) decreases expression of genes related to the regulation of the cell cycle; iii) promotes formation of cardiomyotubes; iv) induces the expression of casein kinase-1-α1, a negative regulator of the canonical WNT signaling pathway; and v) increases the expression of the noncanonicalWNT11, which it has been demonstrated to induce cardiac differentiation during embryonic development and in adult cells. In conclusion, we postulate that vitamin D promotes cardiac differentiation through a negative modulation of the canonical WNT signaling pathway and by upregulating the expression ofWNT11. These results indicate that vitamin D repletion to prevent and/or improve cardiovascular disorders that are linked with abnormal cardiac differentiation, such as post infarction cardiac remodeling, deserve further study.

scholarly journals Mir-186-5p Regulates WNT Signaling Pathway by Targeting TCF4 Transcription Factor

2018 ◽  
Vol 8 (1) ◽  
pp. 132
Author(s):  
Zahra Bayat ◽  
Bahram M. Soltani
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Sw480 Cell ◽  
Sw480 Cell Line ◽  
Sw480 Cells

The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development, tissue homeostasis and differentiation. This pathway is deregulated in many cancers especially colorectal cancer. MiRNAs are a class of small noncoding RNAs that may play a major role in post transcriptional regulation of many genes and signaling pathway such as WNT signaling pathway. Here, we intended to investigate if miR-186-5p is capable of regulating WNT signaling pathway wia suppression TCF4 gene expression. miR-186-5p was bioinformatically predicted as a candidate regulator of TCF4 gene expression and then, in this experimental study, miR-186-5p was overexpressed in SW480 cell line and its increased expression was detected through quantitative reverse transcription polymerase chain reaction (RT-qPCR). The effect of miR-186-5p on WNT pathway was analysied with TOP/FOP flash assay in SW480 cell line. Finally, flow cytometery was used to inves tigate the effect of miR-186-5p overexpression on cell cycle progression in SW480 cell line. miR-186-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the TCF4 mRNA level. TOP/FOP flash assay, confirmed the negative effect of miR-186-5p on the Wnt pathway in SW480 cells. Finally, Overexpression of miR186-5p in SW480 cells resulted in cell cycle arrest in subG1 phase, detected by flow cytometry. Overall, accumulative results indi-cated that miR-186-5p by targeting TCF4 is potentially one of the regulators of the WNT signaling pathway.

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