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Canonical wnt

Yanqin Lu, Xiuzhi Ren, Yanzhou Wang, Ghalib Bardai, Marc Sturm, Yunzhang Dai, Olaf Riess, Yao Zhang, Hu Li, Tianyou Li, Naixiang Zhai, Jian Zhang, Frank Rauch, Jinxiang Han
INTRODUCTION: Biallelic mutations in WNT1 can give rise to a rare form of moderate to severe OI. Here we report on 12 children (age 2 to 16 years; 5 girls) with biallelic WNT1 mutations. METHODS: Genomic DNA was analyzed either by targeted next-generation sequencing or Sanger sequencing. Mutations were modeled on the WNT1 protein structure. The in vitro functional effect of WNT1 mutations on WNT signaling was assessed in HEK293 cells using the topflash reporter assay system...
June 20, 2018: Bone
Marc T Cantwell, Jared S Farrar, Joseph C Lownik, Jeremy A Meier, Moonjung Hyun, Vidisha Raje, Michael R Waters, Francesco S Celi, Daniel H Conrad, Thurl E Harris, Andrew C Larner
Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1 (UCP1). We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage...
June 19, 2018: Cytokine
Dalibel Bravo, Ahmet Salduz, Kristen L Shogren, Madison N Okuno, James L Herrick, Scott H Okuno, Mario Galindo, Andre J van Wijnen, Michael J Yaszemski, Avudaiappan Maran
Osteosarcoma is a malignant bone tumor that occurs mainly in children and adolescents. Because Wnt signaling has been implicated in the pathogenesis of osteosarcoma, we have investigated the circulating and local levels of the Wnt antagonist protein, Secreted Frizzled Related Protein (sFRP) 3, in osteosarcoma patients. Enzyme linked immunosorbent assay (ELISA) analysis of 67 osteosarcoma and age-matched non-diseased control sera showed that sFPR3 protein levels were significantly lower in osteosarcoma than in normal...
June 19, 2018: Gene
Yichen Wang, Priyha Mahesh, Yan Wang, Samuel G Novo, Mahbubul H Shihan, Brielle Hayward-Piatkovskyi, Melinda K Duncan
The appropriate spatial and temporal regulation of canonical Wnt signaling is vital for eye development. However, the literature often conflicts on the distribution of canonical Wnt signaling in the eye. Here, using a sensitive mouse transgenic reporter line, we report a detailed re-evaluation of the spatiotemporal dynamics of canonical Wnt signaling in the developing eye. Canonical Wnt activity was dynamic in the optic vesicle and later in the retina, while it was absent from the ectodermal precursors of the lens and corneal epithelium...
June 19, 2018: Experimental Eye Research
Jin Zhou, Xiaoning Yang, Wei Liu, Chunlan Wang, Yuan Shen, Fengzhi Zhang, Huimin Zhu, Hongji Sun, Jiayun Chen, Johnny Lam, Antonios G Mikos, Changyong Wang
After myocardial infarction (MI), the scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive hydrogel could not only provide mechanical support to the infarcted region, but also synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue. Methods: We created a conductive hydrogel by introducing graphene oxide (GO) nanoparticles into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels...
2018: Theranostics
Hon Yan Kelvin Yip, Chin Wee Tan, Yumiko Hirokawa, Antony Wilks Burgess
Although small intestinal epithelial stem cells form crypts when using intestinal culture conditions, colon stem cells usually form colonospheres. Colon mesenchymal cell feeder layers can stimulate colon crypts to form organoids and produce crypts. We have investigated whether conditioned medium from colon mesenchymal cells can also stimulate colonosphere and organoid cryptogenesis. We prepared conditioned medium (CM) from WEHI-YH2 cells (mouse colon myofibroblasts); the CM stimulated both colonosphere formation and organoid cryptogenesis in vitro...
2018: PloS One
Lika Osugui, Jolanda J de Roo, Vivian Cristina de Oliveira, Ana Clara Pires Sodré, Frank J T Staal, Ana Flavia Popi
Recently several studies demonstrated a role for the Wnt pathway in lymphocyte development and self-renewal of hematopoietic stem cells (HSCs). B-1 cells constitute a separate lineage of B lymphocytes, originating during fetal hematopoiesis, expressing lymphoid and myeloid markers and possessing self-renewal ability, similar to early hematopoietic progenitors and HSCs. A plethora of studies have shown an important role for the evolutionary conserved Wnt pathway in the biology of HSCs and T lymphocyte development...
2018: PloS One
Hong-Yuan Zhang, Ting-Ting Zhang, Jeremiah Ong'achwa Machuki, Li-Juan Wu, Hong Sun
The present study was aimed to characterize the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). IMR90-4 cells were induced to differentiate into cardiomyocytes by temporal modulation of regulators of canonical Wnt signaling. The protein expression of cardiac troponin T (cTnT) was detected by immunofluorescence staining and flow cytometry, and the differentiation rate of hiPSC-CMs was calculated. The action potentials (APs) of hiPSC-CMs were recorded by patch clamp and used to classify different types of cardiomyocytes...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Volodymyr V Balatskyi, Larysa L Macewicz, Ana-Maria Gan, Sergii V Goncharov, Paulina Pawelec, Georgiy V Portnichenko, Tetiana Yu Lapikova-Bryginska, Viktor O Navrulin, Victor E Dosenko, Adam Olichwier, Pawel Dobrzyn, Oksana O Piven
αE-catenin is a component of adherens junctions that link the cadherin-catenin complex to the actin cytoskeleton. The signaling function of this protein was recently revealed. In the present study, we investigated the role of αE-catenin in the pathogenesis of heart failure. We mated αE-catenin conditional knockout mice with αMHC-Cre mice and evaluated their mutant offspring. We found that αE-catenin knockout caused enlargement of the heart and atria, fibrosis, the upregulation of hypertrophic genes, and the dysregulation of fatty acid metabolism via the transcriptional activity of Yap and β-catenin...
June 20, 2018: Pflügers Archiv: European Journal of Physiology
Ling Zhu, Weiyong Shen, Ting Zhang, Ying Wang, Bobak Bahrami, Fanfan Zhou, Mark C Gillies
Müller cells are the primary glia in the retina, playing a critical role in retinal homeostasis and retinal pathology. This study evaluated the canonical Wnt signalling pathway and its downstream effects on retinal degeneration in a transgenic mouse model of inducible Müller cell disruption. Increased expression of the LacZ reporter gene in the retina suggested Wnt signalling had been activated after induced Müller cell disruption. Activation was validated by observing nuclear translocation of β-Catenin...
June 15, 2018: Experimental Eye Research
Amy E O'Connell, Fanny Zhou, Manasvi S Shah, Quinn Murphy, Hannah Rickner, Judith Kelsen, John Boyle, Jefferson J Doyle, Bharti Gangwani, Jay R Thiagarajah, Daniel S Kamin, Jeffrey D Goldsmith, Camilla Richmond, David T Breault, Pankaj B Agrawal
Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs)...
June 4, 2018: American Journal of Human Genetics
Xinjia Cai, Zhigang Yao, Long Li, Junhui Huang
Tumor is the most public health problem. The Wnt signal pathway extensively participates in diverse progresses containing embryonic development, maintenance of homeostasis and tumor pathogenesis. The Wnt signal pathway consists of canonical signal pathway, noncanonical Wnt/PCP pathway and noncanonical Wnt/Ca2+ pathway. The deletion of the ligand of Wnts results in cytoplasmic β-catenin phosphorylation, stopping entry of β-catenin to nuclear in canonical Wnt signaling. Instead, binding of Wnts to frizzled (FZ/FZD) as well as LRP5/6 causes activation of Wnt signal pathways...
2018: International Journal of Biological Sciences
Madhulaxmi Marimuthu, Manoharan Andiappan, Abdul Wahab, M R Muthusekhar, Anandan Balakrishnan, Sambandham Shanmugam
Aim: The aim of this study is to explore the prognostic significance and clinicopathological correlations of the Wnt pathway genes in a cohort of surgically treated patients with oral squamous cell carcinoma (OSCC) patients. Settings and Design: A prospective genetic study on patients with OSCC was carried out during the period from July 2014 to January 2016. Informed consent from patients and institutional ethical approval for the study was obtained and the guidelines were strictly followed for collection of samples...
May 2018: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
Cheng Zhang, Pan Ni, Hafiz Ishfaq Ahmad, M Gemingguli, A Baizilaitibei, D Gulibaheti, Yaping Fang, Haiyang Wang, Akhtar Rasool Asif, Changyi Xiao, Jianhai Chen, Yunlong Ma, Xiangdong Liu, Xiaoyong Du, Shuhong Zhao
Animal domestication gives rise to gradual changes at the genomic level through selection in populations. Selective sweeps have been traced in the genomes of many animal species, including humans, cattle, and dogs. However, little is known regarding positional candidate genes and genomic regions that exhibit signatures of selection in domestic horses. In addition, an understanding of the genetic processes underlying horse domestication, especially the origin of Chinese native populations, is still lacking. In our study, we generated whole genome sequences from 4 Chinese native horses and combined them with 48 publicly available full genome sequences, from which 15 341 213 high-quality unique single-nucleotide polymorphism variants were identified...
2018: Evolutionary Bioinformatics Online
María E Ferrari, María E Bernis, Faye McLeod, Marina Podpolny, Romina P Coullery, Inelia M Casadei, Patricia C Salinas, Silvana B Rosso
The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal development and circuit formation. We previously demonstrated that Wnt7b acts through the scaffold protein Dishevelled (Dvl) to modulate dendrite arborization by activating a Wnt non-canonical signalling pathway...
June 13, 2018: Journal of Cell Science
Erica L L Warkus, Yusuke Marikawa
Fluoxetine is one of the most commonly prescribed antidepressants in the selective serotonin reuptake inhibitor (SSRI) class. Epidemiologic studies have suggested a link between maternal fluoxetine use during pregnancy and an increased incidence of birth defects. However, the mechanisms by which fluoxetine adversely impacts embryonic development are unknown. Here, we used the mouse P19C5 embryoid body (EB) as a 3-dimensional morphogenesis model to investigate the developmental toxicity of fluoxetine. Morphological and molecular changes in P19C5 EBs replicate the processes of axial elongation and patterning seen in early embryos, and these changes are specifically and sensitively altered by exposure to developmental toxicants...
June 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Alexandre Vallée, Bernard L Lévy, Jacques Blacher
PURPOSE OF REVIEW: Heterogeneous causes can determinate hypertension. RECENT FINDINGS: The renin-angiotensin system (RAS) has a major role in the pathophysiology of blood pressure. Angiotensin II and aldosterone are overexpressed during hypertension and lead to hypertension development and its cardiovascular complications. In several tissues, the overactivation of the canonical WNT/β-catenin pathway leads to inactivation of peroxisome proliferator-activated receptor gamma (PPARγ), while PPARγ stimulation induces a decrease of the canonical WNT/β-catenin pathway...
June 9, 2018: Current Hypertension Reports
Sonia Alonso-Martin, Frédéric Auradé, Despoina Mademtzoglou, Anne Rochat, Peter S Zammit, Frédéric Relaix
Muscle satellite cells are the primary source of stem cells for postnatal skeletal muscle growth and regeneration. Understanding genetic control of satellite cell formation, maintenance, and acquisition of their stem cell properties is on-going, and we have identified SOXF (SOX7, SOX17, SOX18) transcriptional factors as being induced during satellite cell specification. We demonstrate that SOXF factors regulate satellite cell quiescence, self-renewal and differentiation. Moreover, ablation of Sox17 in the muscle lineage impairs postnatal muscle growth and regeneration...
June 8, 2018: ELife
Kristin Teiken, Mark Kuehnel, Jan Rehkaemper, Hans Kreipe, Florian Laenger, Kais Hussein, Danny Jonigk
Post-transplant smooth muscle tumors (PTSMTs) are rare mesenchymal neoplasms which occur after solid organ or haematopoietic stem cell transplantation. PTSMT typically consist of Epstein-Barr-virus (EBV)+ smooth muscle-like cells and show an intermediate malignancy. Their main occurrences are visceral organs, especially the liver, but intracranial appearances are described and associated with a poor prognosis. EBV drives the growth of PTSMT; however, the underlying molecular mechanisms still remain unclear...
2018: Clinical Sarcoma Research
Ying Ying Tang, Si Yuan Sheng, Chuan Gang Lu, Yu Qing Zhang, Jian Yong Zou, Yi Yan Lei, Yong Gu, Hai Hong
The canonical Wnt-β-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non-small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3β inhibitor TWS119 has different effects on CD4 and CD8 T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8 stem cell-like memory T cells, and induced CD8 effector T-cell proliferation in TILs...
June 5, 2018: Journal of Immunotherapy
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