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https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#1
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28289266/wnts-synergize-to-activate-%C3%AE-catenin-signaling
#2
Anshula Alok, Zhengdeng Lei, N Suhas Jagannathan, Simran Kaur, Steven G Rozen, Lisa Tucker-Kellogg, David M Virshup
Wnt ligands regulate diverse signaling pathways during development, maintenance of tissue homeostasis, and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. We studied the effect of co-expression of Wnts on the β-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate β-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate β-catenin signaling in multiple cell types...
March 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28273524/altered-bone-microarchitecture-and-gene-expression-profile-due-to-calcium-deficiency-in-a-mouse-model-of-myeloma
#3
Hélène Libouban, Daniel Chappard
It is not clear why patients with an indolent form of multiple myeloma (MM) develop into an aggressive form with poor prognostic. We investigated the effect of a dietary calcium deficiency on tumor growth, osteolysis and gene expression in the 5T2MM murine model. Two groups of C57BL/KaLwRij mice received 5T2MM cells and started a diet with normal (0.8%; "normal-Ca-MM") or low calcium content (0.05%; "low-Ca-MM"). Two control groups (without 5T2MM cells) received either a normal or low calcium diet (normal-Ca and low-Ca groups)...
February 24, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28267633/sclerostin-stimulates-angiogenesis-in-human-endothelial-cells
#4
Angela Oranger, Giacomina Brunetti, Graziana Colaianni, Roberto Tamma, Claudia Carbone, Luciana Lippo, Giorgio Mori, Paolo Pignataro, Nunzio Cirulli, Roberta Zerlotin, Biagio Moretti, Angela Notarnicola, Domenico Ribatti, Maria Grano, Silvia Colucci
Sclerostin, negative regulator of bone formation, has been originally known as an osteocyte product. Recently, it has been also detected in hypertrophic chondrocytes, distinctive cells of avascular cartilage which is invaded by capillaries and then replaced by vascularized bone. Thus, we hypothesized that sclerostin, in addition to its role already known, may exert an angiogenic activity. We first proved that sclerostin increased the proliferation of human umbilical vein endothelial cells (HUVECs), and next, by using the chicken chorioallantoic membrane (CAM) in vivo assay, we demonstrated that it exerts an angiogenic activity similar to that of vascular endothelial growth factor (VEGF)...
March 3, 2017: Bone
https://www.readbyqxmd.com/read/28247948/role-of-wnt-co-receptor-lrp6-in-triple-negative-breast-cancer-cell-migration-and-invasion
#5
Jinlu Ma, Wenyan Lu, Dongquan Chen, Bo Xu, Yonghe Li
The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential Wnt co-receptor of the Wnt/β-catenin signaling pathway. Although studies have shown an increased expression of LRP6 in several types of cancer, its function in tumor development and progression remains to be elucidated. We herein demonstrated that LRP6 expression is up-regulated in human triple negative breast cancer (TNBC) patients and human TNBC cell lines, and that knockdown of LRP6 expression and treatment of recombinant Mesd protein (a specific inhibitor of LRP6) significantly decreased cell migration and invasion of TNBC MDA-MB-231 and BT549 cells...
March 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#6
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223363/auto-inhibition-of-dishevelled-regulated-by-its-extreme-c-terminus-plays-a-distinct-role-in-wnt-beta-catenin-and-wnt-pcp-signaling-pathways
#7
Jing Qi, Ho-Jin Lee, Audrey Saquet, Xiao-Ning Cheng, Ming Shao, Jie J Zheng, De-Li Shi
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ and DEP, whose functions in beta-catenin-dependent canonical Wnt and beta-catenin-independent non-canonical Wnt signaling have been well characterized. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We previously reported that Dvl conformational change triggered by the highly conserved PDZ-binding C-terminus is important for the pathway specificity...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28187755/long-noncoding-rna-papillary-thyroid-carcinoma-susceptibility-candidate-3-ptcsc3-inhibits-proliferation-and-invasion-of-glioma-cells-by-suppressing-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Shujun Xia, Ri Ji, Weiwei Zhan
BACKGROUND: The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown...
February 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28143772/stearoyl-coa-desaturase-promotes-liver-fibrosis-and-tumor-development-in-mice-via-a-wnt-positive-signaling-loop-by-stabilization-of-low-density-lipoprotein-receptor-related-proteins-5-and-6
#9
Keane K Y Lai, Soo-Mi Kweon, Feng Chi, Edward Hwang, Yasuaki Kabe, Reiichi Higashiyama, Lan Qin, Rui Yan, Raymond P Wu, Naoaki Fujii, Samuel French, Jun Xu, Jian-Ying Wang, Ramanchadran Murali, Lopa Mishra, Ju-Seog Lee, James M Ntambi, Hidekazu Tsukamoto
BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed...
January 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28143713/intercellular-transfer-of-mir-126-3p-by-endothelial-microparticles-reduces-vascular-smooth-muscle-cell-proliferation-and-limits-neointima-formation-by-inhibiting-lrp6
#10
Felix Jansen, Tobias Stumpf, Sebastian Proebsting, Bernardo S Franklin, Daniela Wenzel, Philipp Pfeifer, Anna Flender, Theresa Schmitz, Xiaoyan Yang, Bernd K Fleischmann, Georg Nickenig, Nikos Werner
BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial microparticles (EMPs) regulate function and phenotype of target endothelial cells (ECs), but their influence on VSMC biology is unknown. We aim to investigate the role of EMPs in the regulation of vascular smooth muscle cell (VSMC) proliferation and vascular remodeling. METHODS AND RESULTS: Systemic treatment of mice with EMPs after vascular injury reduced neointima formation in vivo...
January 28, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28137581/wnt-%C3%AE-catenin-pathway-modulates-the-tnf-%C3%AE-induced-inflammatory-response-in-bronchial-epithelial-cells
#11
Jaewoong Jang, Yoonju Jung, Seyeon Chae, Sang-In Chung, Seok-Min Kim, Yoosik Yoon
In this study, TNF-α was found to activate the WNT/β-catenin pathway in BEAS-2B human bronchial epithelial cells. Levels of phospho-LRP6, Dvl-2, and phospho-GSK-3β were elevated, while that of Axin was reduced by TNF-α treatment. Nuclear translocation of β-catenin and the reporter activity of a β-catenin-responsive promoter were increased by TNF-α treatment. Under the same experimental conditions, TNF-α activated the NF-κB signaling, which includes the phosphorylation and degradation of IκB and nuclear translocation and target DNA binding of NF-κB, and it was found that an inhibitor of NF-κB activation, JSH-23, inhibited TNF-α-induced Wnt signaling as well as NF-κB signaling...
January 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28130402/connective-tissue-growth-factor-domain-4-amplifies-fibrotic-kidney-disease-through-activation-of-ldl-receptor-related-protein-6
#12
Bryce G Johnson, Shuyu Ren, Gamze Karaca, Ivan G Gomez, Cécile Fligny, Benjamin Smith, Ayla Ergun, George Locke, Benbo Gao, Sebastian Hayes, Scott MacDonnell, Jeremy S Duffield
Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction...
January 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28123855/microrna-454-shows-anti-angiogenic-and-anti-metastatic-activity-in-pancreatic-ductal-adenocarcinoma-by-targeting-lrp6
#13
Yue Fan, Chenye Shi, Tianyu Li, Tiantao Kuang
Our previous work has shown that microRNA-454 (miR-454) can inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) by blocking the recruitment of bone marrow-derived macrophages. In the present study, we aimed to explore its role in the proliferation, invasion, and pro-angiogenic activity of PDAC cells in vitro and lung metastasis in vivo. PANC-1 and MiaPaCa-2 cells were transfected with a miR-454-expressing plasmid and tested for cell proliferation, colony formation, cell cycle distribution, invasion, and pro-angiogenic activity...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28102559/effect-of-bone-like-hydroxyapatite-poly-amino-acid-loaded-with-rifapentine-microspheres-on-bone-and-joint-tuberculosis-in-vitro
#14
Yuwu Liu, Dianming Jiang
Rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (RPMs)-loaded bone-like hydroxyapatite/poly amino acid (BHA/PAA) is effective in curing Staphylococcus aureus-induced chronic osteomyelitis. This study continues to investigate the effect of RPM-loaded BHA/PAA on the bacterial growth of Mycobacterium tuberculosis (MTB), cell proliferation and differentiation in MTB H37Rv-infected MG63 cells. Furthermore, whether Wnt/β-catenin signaling pathway was activated by RPM-loaded BHA/PAA was explored. We found the bactec growth index of H37Rv was significantly inhibited by RPM-loaded BHA/PAA...
January 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28077837/curcumin-inhibits-gastric-carcinoma-cell-growth-and-induces-apoptosis-by-suppressing-the-wnt-%C3%AE-catenin-signaling-pathway
#15
Ruzhen Zheng, Qinghua Deng, Yuehua Liu, Pengjun Zhao
BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay...
January 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28069902/wnt-regulation-of-embryonic-development-likely-involves-pathways-independent-of-nuclear-ctnnb1
#16
Paula Tribulo, James I Moss, Manabu Ozawa, Zongliang Jiang, Xiuchun Cindy Tian, Peter J Hansen
The bovine was used to examine the potential for WNT signaling to affect the preimplantation embryo. Expression of seven key genes involved in canonical WNT signaling declined to a nadir at the morula or blastocyst stage. Expression of 80 genes associated with WNT signaling in the morula and inner cell mass (ICM) and trophectoderm (TE) of the blastocyst was also evaluated. Many genes associated with WNT signaling were characterized by low transcript abundance. Seven genes were different between ICM and TE, and all of them were overexpressed in TE as compared to ICM, including WNT6, FZD1, FZD7, LRP6, PORCN, APC and SFRP1 Immunoreactive CTNNB1 was localized primarily to the plasma membrane at all stages examined from the 2-cell to blastocyst stages of development...
April 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#17
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28056051/mapping-the-interactome-of-a-major-mammalian-endoplasmic-reticulum-heat-shock-protein-90
#18
Feng Hong, Saleh Mohammad Rachidi, Debbie Lundgren, David Han, Xiu Huang, Hongyu Zhao, Yayoi Kimura, Hisashi Hirano, Osamu Ohara, Heichiiro Udono, Songdong Meng, Bei Liu, Zihai Li
Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96...
2017: PloS One
https://www.readbyqxmd.com/read/28052259/conformational-freedom-of-the-lrp6-ectodomain-is-regulated-by-n-glycosylation-and-the-binding-of-the-wnt-antagonist-dkk1
#19
Kyoko Matoba, Emiko Mihara, Keiko Tamura-Kawakami, Naoyuki Miyazaki, Shintaro Maeda, Hidenori Hirai, Samuel Thompson, Kenji Iwasaki, Junichi Takagi
LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28042322/chromatin-remodeling-factor-lsh-is-upregulated-by-the-lrp6-gsk3%C3%AE-e2f1-axis-linking-reversely-with-survival-in-gliomas
#20
Desheng Xiao, Jun Huang, Yu Pan, Hao Li, Chunyan Fu, Chao Mao, Yan Cheng, Ying Shi, Ling Chen, Yiqun Jiang, Rui Yang, Yating Liu, Jianhua Zhou, Ya Cao, Shuang Liu, Yongguang Tao
The signaling pathway-based stratification in chromatin modification could predict clinical outcome more reliably than morphology-alone-based classification schemes in gliomas. Here we reported a role of the chromatin-remodeling factor lymphoid-specific helicase (LSH) in gliomas. Among astrocytomas of grade I to III and glioblastoma of grade IV, LSH were almost completely expressed in all cases, and strongly correlated with astrocytomas progression and poor prognosis of patients with astrocytomas and glioblastoma...
2017: Theranostics
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