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https://www.readbyqxmd.com/read/27932350/role-of-noncanonical-wnts-signaling-pathway-in-human-aortic-valve-calcification
#1
Isabella Albanese, Bin Yu, Hamood Al-Kindi, Bianca Barratt, Leah Ott, Mohammad Al-Refai, Benoit de Varennes, Dominique Shum-Tim, Marta Cerruti, Ophélie Gourgas, Eric Rhéaume, Jean-Claude Tardif, Adel Schwertani
OBJECTIVE: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. APPROACH AND RESULTS: Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs)...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27927230/molecular-control-of-nitric-oxide-synthesis-through-enos-and-caveolin-1-interaction-regulates-osteogenic-differentiation-of-adipose-derived-stem-cells-by-modulation-of-wnt-%C3%AE-catenin-signaling
#2
Nadeeka Bandara, Saliya Gurusinghe, Shiang Yong Lim, Haying Chen, Shuangfeng Chen, Dawei Wang, Bryan Hilbert, Le-Xin Wang, Padraig Strappe
BACKGROUND: Nitric oxide (NO) plays a role in a number of physiological processes including stem cell differentiation and osteogenesis. Endothelial nitric oxide synthase (eNOS), one of three NO-producing enzymes, is located in a close conformation with the caveolin-1 (CAV-1(WT)) membrane protein which is inhibitory to NO production. Modification of this interaction through mutation of the caveolin scaffold domain can increase NO release. In this study, we genetically modified equine adipose-derived stem cells (eASCs) with eNOS, CAV-1(WT), and a CAV-1(F92A) (CAV-1(WT) mutant) and assessed NO-mediated osteogenic differentiation and the relationship with the Wnt signaling pathway...
December 7, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27923152/hydronephrosis-in-the-wnt5a-ablated-kidney-is-caused-by-an-abnormal-ureter-bladder-connection
#3
Kangsun Yun, Alan O Perantoni
The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme...
December 3, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27916087/-the-regulatory-role-of-wnt-signaling-pathway-in-the-proliferation-and-activation-of-memory-t-cells
#4
Lei Luo, Guangheng Luo, Qian Fang, Shan Huang, Hui Chen
Objective To study the regulatory effect of Wnt signaling pathway on the activation and proliferation of memory T cells (TMs). Methods We established the mouse model of skin allograft transplantation (BALB/c-C57BL/6), and then we sorted and cultured immature dendritic cells (imDCs), mature dendritic cells (mDCs) and TMs from the C57BL/6 mice by immunomagnetic bead cell sorting. The imDCs or mDCs loading antigens from BALB/c mice were co-cultured with TMs in a 96-well plate or Transwell(TM) plate (MLR). The (3)H-TdR was used to detect the proliferation of TMs...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27913393/epigenetically-activated-wnt5a-promotes-glioblastoma-progression
#5
(no author information available yet)
WNT5A signaling drives an endothelial cell transcriptional program in GBM stem cells.
December 2, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#6
J Yu, L Chen, B Cui, C Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895670/wnt5a-increases-properties-of-lung-cancer-stem-cells-and-resistance-to-cisplatin-through-activation-of-wnt5a-pkc-signaling-pathway
#7
Jiali Yang, Kangjian Zhang, Jing Wu, Juan Shi, Jing Xue, Jing Li, Juan Chen, Yongzhao Zhu, Jun Wei, Jinxi He, Xiaoming Liu
The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27895173/human-regulatory-t-cells-mediate-transcriptional-modulation-of-dendritic-cell-function
#8
Emily Mavin, Lindsay Nicholson, Syed Rafez Ahmed, Fei Gao, Anne Dickinson, Xiao-Nong Wang
Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and stimulatory function. Current knowledge on the functional impact of semimature DC is limited to CD4(+) T cell proliferation and cytokine production. Little is known about the molecular basis underpinning the functional effects of Treg-treated DC (Treg-DC). We present novel evidence that Treg-DC skewed CD4(+) naive T cell polarization toward a regulatory phenotype and impaired CD8(+) T cell allo-reactive responses, including their ability to induce target tissue damage in a unique in vitro human graft-versus-host disease skin explant model...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895148/trpc5-regulates-differentiation-through-the-ca2-wnt5a-signal-pathway-in-colorectal-cancer
#9
Zhen Chen, Chunlei Tang, Yaodan Zhu, Mingxu Xie, Dongxu He, Qiongxi Pan, Peng Zhang, Dong Hua, Teng Wang, Linfang Jin, Xiaowei Qi, Yifei Zhu, Xiaoqiang Yao, Jian Jin, Xin Ma
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca(2+) channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca(2+)]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness...
November 28, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27892464/wnt5a-induces-renal-aqp2-expression-by-activating-calcineurin-signalling-pathway
#10
Fumiaki Ando, Eisei Sohara, Tetsuji Morimoto, Naofumi Yui, Naohiro Nomura, Eriko Kikuchi, Daiei Takahashi, Takayasu Mori, Alain Vandewalle, Tatemitsu Rai, Sei Sasaki, Yoshiaki Kondo, Shinichi Uchida
Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27882931/plasma-sfrp5-and-adiponectin-levels-in-relation-to-blood-pressure-among-obese-children
#11
C Yin, H Chu, H Li, Y Xiao
The aim was to clarify the associations of five adipocytokines: Sfrp5, Wnt5a, adiponectin, chemerin and high-sensitivity C-reactive protein (hsCRP) with blood pressure (BP), and to examine whether BP can be influenced by changes in these adipocytokines in obese children after a 6-month lifestyle intervention. We conducted a cross-sectional study in 263 obese children and performed a 6-month lifestyle intervention in a subgroup of 89 obese children with hypertension. Anthropometric data, adiponectin, chemerin, Sfrp5 and Wnt5a were assessed at baseline and after 6-month lifestyle intervention...
November 24, 2016: Journal of Human Hypertension
https://www.readbyqxmd.com/read/27882132/silencing-of-wnt5a-prevents-interleukin-1%C3%AE-induced-collagen-type-ii-degradation-in-rat-chondrocytes
#12
Shiping Shi, Zhentao Man, Wei Li, Shui Sun, Wei Zhang
Osteoarthritis (OA) is a joint disease, and few treatments to date have been able to delay OA progression. The degradation of collagen type II (COL2) in the cartilage matrix is an important initiating factor for OA progression; the upregulation of Wnt5a protein activates COL2 degradation. In the present study, small interfering RNA of Wnt-5a was delivered by a lentiviral vector (LV-Wnt5a-RNAi) to silence Wnt-5a mRNA and prevent COL2 degradation. To determine the function of LV-Wnt5a-RNAi, the OA chondrocyte model (OA-like chondrocytes) were constructed using interleukin (IL)-1β...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27878554/the-involvement-of-the-decrease-of-astrocytic-wnt5a-in-the-cognitive-decline-in-minimal-hepatic-encephalopathy
#13
Saidan Ding, Zhu Xu, Jianjing Yang, Leping Liu, Xueli Huang, Xuebao Wang, Qichuan Zhuge
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27876017/increased-wnt5a-in-squamous-cell-lung-carcinoma-inhibits-endothelial-cell-motility
#14
J Rapp, E Kiss, M Meggyes, E Szabo-Meleg, D Feller, G Smuk, T Laszlo, V Sarosi, T F Molnar, K Kvell, J E Pongracz
BACKGROUND: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process...
November 23, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27863244/epigenetic-activation-of-wnt5a-drives-glioblastoma-stem-cell-differentiation-and-invasive-growth
#15
Baoli Hu, Qianghu Wang, Y Alan Wang, Sujun Hua, Charles-Etienne Gabriel Sauvé, Derrick Ong, Zheng D Lan, Qing Chang, Yan Wing Ho, Marta Moreno Monasterio, Xin Lu, Yi Zhong, Jianhua Zhang, Pingna Deng, Zhi Tan, Guocan Wang, Wen-Ting Liao, Lynda J Corley, Haiyan Yan, Junxia Zhang, Yongping You, Ning Liu, Linbo Cai, Gaetano Finocchiaro, Joanna J Phillips, Mitchel S Berger, Denise J Spring, Jian Hu, Erik P Sulman, Gregory N Fuller, Lynda Chin, Roeland G W Verhaak, Ronald A DePinho
Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs)...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27859213/role-of-wnt5a-in-the-pathogenesis-of-inflammatory-diseases
#16
REVIEW
Mehran Pashirzad, Mojtaba Shafiee, Farzad Rahmani, Reihane Behnam-Rassouli, Fatemeh Hoseinkhani, Mikhail Ryzhikov, Maryam Moradi Binabaj, Mohammad Reza Parizadeh, Amir Avan, Seyed Mahdi Hassanian
Wnt5a initiates pro-inflammatory responses through activation of non-canonical Wnt signaling pathway. Pro-inflammatory functions of Wnt5a trigger pro-inflammatory signaling cascades and increase secretion of pro-inflammatory cytokines and chemokines. Wnt5a as a potent signaling molecule is strongly implicated in a number of diseases including cancer, diabetes, metabolic disorders, and of special interest in this review, inflammatory diseases. This review summarizes the role of Wnt5a in the pathogenesis of inflammatory diseases including atherosclerosis, rheumatoid arthritis, psoriasis vulgaris and sepsis, promoting greater understanding and clinical management of these diseases...
November 11, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27843938/wnt-%C3%AE-catenin-signaling-promotes-the-maturation-of-mast-cells
#17
Tomoko Yamaguchi, Misae Nishijima, Katsuhisa Tashiro, Kenji Kawabata
Mast cells play an important role in the pathogenesis of allergic diseases. Immature mast cells migrate into peripheral tissues from the bone marrow and undergo complete maturation. Interestingly, mast cells have characteristics similar to hematopoietic stem cells (HSCs), such as self-renewal and c-kit expression. In HSCs, Wnt signaling is involved in their maintenance and differentiation. On the other hand, the relation between Wnt signaling and mast cell differentiation is poorly understood. To study whether Wnt signals play a role in the maturation of mast cells, we studied the effect of Wnt proteins on mast cell maturation of bone marrow-derived mast cells (BMMCs)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27831944/receptor-for-advanced-glycation-end-product-blockade-enhances-the-chemotherapeutic-effect-of-cisplatin-in-tongue-squamous-cell-carcinoma-by-reducing-autophagy-and-modulating-the-wnt-pathway
#18
Ziming Zhao, Hongyu Wang, Liao Zhang, Xifan Mei, Jing Hu, Keqiang Huang
Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blockade alone by flow cytometry...
November 9, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27828711/wnt5a-deficiency-regulates-inflammatory-cytokine-secretion-polarization-and-apoptosis-in-mycobacterium-tuberculosis-infected-macrophages
#19
Deming Chen, Guobao Li, Xiangdong Fu, Pei Li, Jie Zhang, Lan Luo
Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (MTB), is one of the global public health catastrophes. Wnt signaling has recently been identified to exert immunoregulatory functions in a variety of inflammatory and infectious diseases, including tuberculosis. The opposite expression of Wnt5a in human and mice during MTB infection drives us to explore the roles and biological significances of reduced Wnt5a for MTB-treated mice. In our study, the reduction of WNT5A in MTB-treated mice lung tissues or MTB-infected mice bone marrow-derived macrophages (BM-Mø) was in a dose- and time-dependent manner...
November 9, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27826714/exendin-4-promotes-pancreatic-%C3%AE-cell-proliferation-via-inhibiting-the-expression-of-wnt5a
#20
Xinger Wu, Weiwei Liang, Hongyu Guan, Juan Liu, Liehua Liu, Hai Li, Xiaoying He, Jing Zheng, Jie Chen, Xiaopei Cao, Yanbing Li
Exendin-4, a glucagon-like peptide-1 receptor agonist, is currently regarded as an effective therapeutic strategy for type-2 diabetes. Previous studies indicated that exendin-4 promoted β cell proliferation. However, the underlying mechanisms remain largely unknown. Recently it was reported that exendin-4 promoted pancreatic β cell proliferation by regulating the expression level of Wnt4. The present study was designed to investigate whether other Wnt isoforms take part in accommodation of β-cell proliferation...
November 9, 2016: Endocrine
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