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https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#1
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#2
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28292419/wnt-pcp-instructions-for-cilia-in-left-right-asymmetry
#3
Jun Wu, Marek Mlodzik
Wnt-Frizzled/planar cell polarity (PCP) signaling establishes cell orientation within the epithelial plane, but whether Wnts are instructive or permissive is debated. Reporting in Developmental Cell, Minegishi et al. (2017) uncover an instructive link from Wnt5a/b gradients to PCP-factor-regulated polarized cilia positioning that is essential to mouse embryo left-right asymmetry establishment.
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28273499/secreted-frizzled-related-protein-2-mediated-cancer-events-friend-or-foe
#4
REVIEW
Yanhui Liu, Qun Zhou, Dexi Zhou, Cheng Huang, Xiaoming Meng, Jun Li
Secreted frizzled-related protein (SFRP)2, an identified member of the SFRPs family of molecules, is often methylated in human cancers and its down-regulation is closely related to Wnt signaling activity and tumor progression. Although the blocker of the Wnt signaling has not been fully used in clinical trial, interest has been further enhanced by the realization of SFRPs' potential as targets to modulate Wnt signaling and cancer cell growth. Emerging evidence showed that SFRP2 was an anti-oncogene, however, a steady flow of research has indicated that it may also have tumor promotion effects in some cancer types...
January 9, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28267592/sfrp4-signalling-of-apoptosis-and-angiostasis-uses-nitric-oxide-cgmp-permeability-axis-of-endothelium
#5
Uttara Saran, Mani Krishna Priya, Uma Maheswari Balaguru, Akila Swaminathan, Shunmugam Nagarajan, Arun Dharmarajan, Suvro Chatterjee
Nitric oxide (NO) plays a critical role in endothelial functions such as cellular migration, vascular permeability and angiogenesis. Angiogenesis, the formation of new blood vessels from "pre-existing" ones is a carefully regulated process and essential during reproduction, development and wound healing. Previously our lab group reported that Secreted Frizzled-Related Protein 4 (sFRP4) could inhibit angiogenesis in both in vitro and in vivo conditions. sFRP4 belongs to a family of secreted glycoproteins that function as antagonists of the canonical Wnt signalling pathway...
March 3, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28251982/-3d-structure-of-dkk1-indicates-its-involvement-in-both-canonical-and-non-canonical-wnt-pathways
#6
S Khalili, M J Rasaee, T Bamdad
Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28247840/microrna-520b-suppresses-proliferation-migration-and-invasion-of-spinal-osteosarcoma-cells-via-downregulation-of-frizzled-8
#7
Jin Wang, Wenquan Pang, Zhenbai Zuo, Wenyan Zhang, Weidong He
Spinal osteosarcoma (OS) is a malignant tumor with poor outcomes. MicroRNA (miR)-520b acts as a cancer suppressor in various cancer types. Due to the limited literatures in OS, we aimed to identify the role of miR-520b in OS. The miR-520b levels in clinical spinal OS tissues and adjacent non-tumor tissues as well as cell lines were assessed. The effect of miR-520b on cell proliferation, migration, invasion and frizzled-8 (FZD8) degradation were all evaluated. Finally, the alterations of key proteins involved in Wnt/β-catenin pathway were assessed by Western blot analysis...
February 28, 2017: Oncology Research
https://www.readbyqxmd.com/read/28245136/reduced-frizzled-receptor-4-expression-prevents-wnt-%C3%AE-catenin-driven-alveolar-lung-repair-in-copd
#8
Wioletta Skronska-Wasek, Kathrin Mutze, Hoeke A Baarsma, Ken R Bracke, Hani N Alsafadi, Mareike Lehmann, Rita Costa, Mariano Stornaiuolo, Ettore Novellino, Guy G Brusselle, Darcy E Wagner, Ali Ö Yildirim, Melanie Königshoff
RATIONALE: Chronic obstructive pulmonary disease (COPD), in particular emphysema, is characterized by loss of parenchymal alveolar tissue and impaired tissue repair. WNT/β-catenin signaling is reduced in COPD, however, the mechanisms thereof, specifically the role of WNT receptors Frizzled (FZD), remains unexplored. OBJECTIVE: To identify and functionally characterize specific FZD receptors that control downstream WNT signaling in impaired lung repair in COPD. METHODS: FZD receptor expression was analyzed in lung homogenates and primary alveolar epithelial type II (ATII) cells of never-smokers, smokers, and COPD patients, as well as two experimental emphysema models by qRT-PCR, immunoblotting, and immunofluorescence...
February 28, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28236965/ror-family-receptor-tyrosine-kinases
#9
Sigmar Stricker, Verena Rauschenberger, Alexandra Schambony
ROR-family receptor tyrosine kinases form a small subfamily of receptor tyrosine kinases (RTKs), characterized by a conserved, unique domain architecture. ROR RTKs are evolutionary conserved throughout the animal kingdom and act as alternative receptors and coreceptors of WNT ligands. The intracellular signaling cascades activated downstream of ROR receptors are diverse, including but not limited to ROR-Frizzled-mediated activation of planar cell polarity signaling, RTK-like signaling, and antagonistic regulation of WNT/β-Catenin signaling...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28218291/a-pan-cancer-analysis-of-secreted-frizzled-related-proteins-re-examining-their-proposed-tumour-suppressive-function
#10
Krista Marie Vincent, Lynne-Marie Postovit
Secreted frizzled-related proteins (SFRPs), containing five family members (SFRPs 1-5) are putative extracellular Wnt inhibitors. Given their abilities to inhibit Wnt signalling, as well as the loss of SFRP1 in many cancers, this family is generally considered to be tumour suppressive. In this study we analyzed gene expression, promoter methylation and survival data from over 8000 tumour and normal samples from 29 cancers in order to map the context-specific associations of SFRPs 1-5 with patient survival, gene silencing and gene expression signatures...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#11
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28209772/maternal-smoke-exposure-decreases-mesenchymal-proliferation-and-modulates-rho-gtpase-dependent-actin-cytoskeletal-signaling-in-fetal-lungs
#12
Uchenna Unachukwu, Jordis Trischler, Monica Goldklang, Rui Xiao, Jeanine D'Armiento
The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m(3)) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28208209/the-emergence-of-tnik-inhibitors-in-cancer-therapeutics
#13
REVIEW
Tesshi Yamada, Mari Masuda
The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene. Aberrant activation of Wnt signaling is a major force driving colorectal carcinogenesis. Several therapeutics targeting Wnt pathway molecules, including porcupine, frizzled receptors, and tankyrases, have been developed, but none of them have yet been incorporated into clinical practice...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28197104/angled-growth-of-the-dental-lamina-is-accompanied-by-asymmetrical-expression-of-the-wnt-pathway-receptor-frizzled-6
#14
Iveta Putnová, Hana Dosedělová, Vitezslav Bryja, Marie Landová, Marcela Buchtová, Jan Štembírek
Frizzled 6 (FZD6) belongs to a family of proteins that serve as receptors in the WNT signaling pathway. FZD6 plays an important role in the establishment of planar cell polarity in many embryonic processes such as convergent extension during gastrulation, neural tube closure, or hair patterning. Based on its role during hair development, we hypothesized that FZD6 may have similar expression pattern and function in the dental lamina, which is also a distinct epithelial protrusion growing characteristically angled into the mesenchyme...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28178355/effects-of-exercise-training-on-circulating-levels-of-dickkpof-1-and-secreted-frizzled-related-protein-1-in-breast-cancer-survivors-a-pilot-single-blind-randomized-controlled-trial
#15
Tae Ho Kim, Jae Seung Chang, Kyu-Sang Park, Jeeyeon Park, Nahyun Kim, Jong In Lee, In Deok Kong
BACKGROUND: Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28177772/frizzled-gene-expression-and-negative-regulation-of-canonical-wnt-%C3%AE-catenin-signaling-in-mouse-f9-teratocarcinoma-cells
#16
Gregory Golenia, Mohamed I Gatie, Gregory M Kelly
Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT-β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin-TCF-LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the 10 Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knock-down and ectopically express the Fzd7 message, respectively...
September 13, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28153008/correlation-of-blood-bone-turnover-biomarkers-and-wnt-signaling-antagonists-with-as-dish-opll-and-oyl
#17
Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Lih-Huei Chen, Chuen-Yung Yang, An-Ni Chung, Meng-Ling Lu, Tsung-Ting Tsai, Po-Liang Lai, Wen-Jer Chen
BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL)...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#18
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28147310/colorectal-cancer-cells-suppress-cd4-t-cells-immunity-through-canonical-wnt-signaling
#19
Xuan Sun, Suoning Liu, Daguang Wang, Yang Zhang, Wei Li, Yuchen Guo, Hua Zhang, Jian Suo
Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28126591/fzd10-g%C3%AE-13-signalling-axis-points-to-a-role-of-fzd10-in-cns-angiogenesis
#20
Belma Hot, Jana Valnohova, Elisa Arthofer, Katharina Simon, Jaekyung Shin, Mathias Uhlén, Evi Kostenis, Jan Mulder, Gunnar Schulte
Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10 remains the most enigmatic. FZD10 shows homology to FZD4 and FZD9 and was previously implicated in both β-catenin-dependent and -independent signalling. In normal tissue, FZD10 levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10 as a receptor interacting with and signalling through the heterotrimeric G protein Gα13 but not Gα12, Gαi1, GαoA, Gαs, or Gαq...
January 24, 2017: Cellular Signalling
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