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macrophage catenin

Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
November 21, 2016: Journal of Clinical Investigation
Hsin-Ling Yang, Yu-Cheng Tsai, Mallikarjuna Korivi, Chia-Ting Chang, You-Cheng Hseu
Lucidone, which comprises a naturally occurring cyclopentenedione, has been investigated for its in vitro and in vivo wound healing properties, and the underlying molecular signaling cascades in the wound healing mechanism have been elucidated. We demonstrated the cell-/dose-specific responses of lucidone (0.5-8μM) on proliferation and migration/invasion of keratinocyte HaCaT and fibroblast Hs68 cells. In keratinocytes, lucidone-induced nuclear translocation of β-catenin was accompanied by increased transcriptional target genes, including c-Myc and cyclin-D1, through GSK3β-dependent pathway...
January 2017: Biochimica et Biophysica Acta
Subhrajit Saha, Evelyn Aranda, Yoku Hayakawa, Payel Bhanja, Safinur Atay, N Patrik Brodin, Jiufeng Li, Samuel Asfaha, Laibin Liu, Yagnesh Tailor, Jinghang Zhang, Andrew K Godwin, Wolfgang A Tome, Timothy C Wang, Chandan Guha, Jeffrey W Pollard
WNT/β-catenin signalling is crucial for intestinal homoeostasis. The intestinal epithelium and stroma are the major source of WNT ligands but their origin and role in intestinal stem cell (ISC) and epithelial repair remains unknown. Macrophages are a major constituent of the intestinal stroma. Here, we analyse the role of macrophage-derived WNT in intestinal repair in mice by inhibiting their release using a macrophage-restricted ablation of Porcupine, a gene essential for WNT synthesis. Such Porcn-depleted mice have normal intestinal morphology but are hypersensitive to radiation injury in the intestine compared with wild-type (WT) littermates...
October 13, 2016: Nature Communications
Yasuhiko Koga, Takahiro Satoh, Kyoichi Kaira, Masashi Koka, Takeshi Hisada, Junko Hirato, Bolag Altan, Masakiyo Yatomi, Akihiro Ono, Yosuke Kamide, Yasuo Shimizu, Haruka Aoki-Saito, Hiroaki Tsurumaki, Kimihiro Shimizu, Akira Mogi, Tamotsu Ishizuka, Masanobu Yamada, Kunio Dobashi
OBJECTIVES: Studies have shown that inhaled mine dust, such as asbestos, can be translocated to various organs including the lymph nodes. Recently, we have established a protocol that enables us to identify inhaled elements using paraffin embedded lung specimens by in-air microparticle-induced X-ray emission (micro-PIXE). However, little research has examined the concentration of these inhaled fibers in various organs or the mechanisms of their translocation. In this study, we compared the concentration of inhaled fibers in the lung parenchyma to the concentration in the hilar lymph node as well as to determine the elemental spatial distribution of the inhaled fibers in a patient with occupational asbestos exposure...
November 2016: Environmental Health and Preventive Medicine
Joseph A Sennello, Alexander V Misharin, Annette S Flozak, Sergejs Berdnikovs, Paul Cheresh, John Varga, David W Kamp, G R Scott Budinger, Cara J Gottardi, Anna P Lam
Previous studies established that attenuating Wnt/β-catenin signaling limits lung fibrosis in the bleomycin mouse model of this disease, but the contribution of this pathway to distinct lung cell phenotypes relevant to tissue repair and fibrosis remains incompletely understood. Using microarray analysis, we found that bleomycin-injured lungs from mice that lack the Wnt co-receptor Lrp5 and exhibit reduced fibrosis, showed enrichment for pathways related to extracellular matrix processing, immunity, and lymphocyte proliferation, suggesting the contribution of an immune-matrix remodeling axis relevant to fibrosis...
September 26, 2016: American Journal of Respiratory Cell and Molecular Biology
Purnima Gupta, Supriya Srivastav, Shriya Saha, Pijush K Das, Anindita Ukil
In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival...
November 1, 2016: Cell Death and Differentiation
Alireza Milani, Marzieh Basirnejad, Sepideh Shahbazi, Azam Bolhassani
Carotenoids and retinoids have several similarities in biological activities such as antioxidant properties, the inhibition of malignant tumor growth, and the induction of apoptosis. Supplementation with carotenoids can influence cell growth regulation, and modulate gene expression and immune response. Epidemiologic studies have shown the correlation of high carotenoid intake from food sources with reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular or eye diseases. Cancer chemoprevention by dietary carotenoids involves some approaches including gap junctional intercellular communication (GJIC), growth factor signaling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, Wnt/β-Catenin pathway, and inflammatory cytokines...
September 16, 2016: British Journal of Pharmacology
Yue Shao, Qianqian Zheng, Wei Wang, Na Xin, Xiaowen Song, Chenghai Zhao
Wnt5a is implicated in development and tissue homeostasis by activating β-catenin-independent pathway. Excessive production of Wnt5a is related to some human diseases. Macrophage recruitment is a character of inflammation and cancer, therefore macrophage-derived Wnt5a is supposed to be a player in these conditions. Actually, macrophage-derived Wnt5a maintains macrophage immune function, stimulates pro-inflammatory cytokine release, and induces angiogenesis and lymphangiogenesis. Furthermore, macrophage-derived Wnt5a is involved in insulin resistance, atherosclerosis and cancer...
September 6, 2016: Oncotarget
Ga Bin Park, Yoon Hee Chung, Ji Hee Gong, Dong-Hoon Jin, Daejin Kim
Glycogen synthase kinase-3β (GSK-3β) in cancer cells is a critical regulatory component of both cellular metabolism and epithelial-mesenchymal transition (EMT) processes via regulation of the β-catenin/E-cadherin and phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Lipogenesis of cancer cells also plays a critical role in survival and metastasis. We investigated the role of GSK-3β-mediated intracellular fatty acid synthesis to control EMT in TLR4-activated colorectal cancer cells and the underlying regulatory mechanism...
September 5, 2016: International Journal of Oncology
Pavan Patel, Steven E Schutzer, Nikolaos Pyrsopoulos
Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis. Though treatment modalities are available, mortality from this cancer remains high. Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival. Immunotherapy, with modern pharmacologic developments, is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation...
August 15, 2016: World Journal of Gastrointestinal Pathophysiology
Jacob J Orme, Yong Du, Kamala Vanarsa, Tianfu Wu, Anne B Satterthwaite, Chandra Mohan
Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus...
2016: PloS One
Shi Yue, Jianjun Zhu, Ming Zhang, Changyong Li, Xingliang Zhou, Min Zhou, Michael Ke, Ronald W Busuttil, Qi-Long Ying, Jerzy W Kupiec-Weglinski, Qiang Xia, Bibo Ke
: Heat shock transcription factor 1 (HSF1) has been implicated in the differential regulation of cell stress and disease states. β-catenin activation is essential for immune homeostasis. However, little is known about the role of macrophage HSF1-β-catenin signaling in the regulation of NLRP3 inflammasome activation during ischemia/reperfusion (I/R) injury (IRI) in the liver. This study investigated the functions and molecular mechanisms by which HSF1-β-catenin signaling influenced NLRP3-mediated innate immune response in vivo and in vitro...
November 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Emelie Karnevi, Ann H Rosendahl, Katarzyna Said Hilmersson, Moin A Saleem, Roland Andersson
Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased...
August 15, 2016: Experimental Cell Research
Sara Al-Ghadban, Samira Kaissi, Fadia R Homaidan, Hassan Y Naim, Marwan E El-Sabban
Inflammatory bowel disease (IBD) involves functional impairment of intestinal epithelial cells (IECs), concomitant with the infiltration of the lamina propria by inflammatory cells. We explored the reciprocal paracrine and direct interaction between human IECs and macrophages (MΦ) in a co-culture system that mimics some aspects of IBD. We investigated the expression of intercellular junctional proteins in cultured IECs under inflammatory conditions and in tissues from IBD patients. IECs establish functional gap junctions with IECs and MΦ, respectively...
2016: Scientific Reports
Kishan Bellamkonda, Naveen Kumar Chandrashekar, Janina Osman, Benson Chellakkan Selvanesan, Sayeh Savari, Anita Sjölander
BACKGROUND: Colorectal cancer is one of the most common types of cancers worldwide. Recent studies have identified cancer-initiating cells (CICs) as a subgroup of replication-competent cells in the development of colorectal cancer. Although it is understood that an inflammation-rich tumor microenvironment presumably supports CIC functions, the contributory factors are not very well defined. The present study advances our understanding of the role of the eicosanoids leukotriene D4 (LTD4) and prostaglandin E2 (PGE2) in the tumorigenic ability of CICs and investigates the consequential changes occurring in the tumor environment that might support tumor growth...
2016: BMC Cancer
X R Tian, X L Tian, H F Wang, Q Chang, R J Huo, D L Ying, G P Zheng
OBJECTIVE: To investigate the regulation effect of β-catenin pathway on transforming growth factor beta1 (TGF-β1) induced pulmonary pro-fibrosis. METHODS: The rat alveolar typeⅡ cells (RLE-6TN) were divided into four groups: A1.control group; B1.TGF-β1 group was treated with 5 μg/L TGF-β1; C1.pcDNA+ TGF-β1 group was transiently transfected with eukaryotic expression vector pcDNA3.0 (pcDNA) and followed by TGF-β1 treatment (5 μg/L); D1.F-(β-TrCP)-Ecad+ TGF-β1 group was transiently transfected with β-catenin protein knockout vector [F-(β-TrCP)-Ecad] and followed by TGF-β1 treatment (5 μg/L)...
June 28, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jie Mao, Duowei Wang, Zhuo Wang, Wei Tian, Xianjing Li, Jingjing Duan, Yun Wang, Hongbao Yang, Linjun You, Yan Cheng, Jinsong Bian, Zhen Chen, Yong Yang
Combretastatin A-1 phosphate (CA1P) is a microtubule polymerization inhibitor that binds to the colchicine-binding site of tubulin. We demonstrated that CA1P has outstanding anti-cancer activity against hepatocellular carcinoma (HCC) in vitro and in vivo. As determined by fluorescence staining and western blots (WBs), CA1P induced reactive oxygen species (ROS) accumulation and apoptosis in HepG2 cells with a down-regulation of Mcl-1. Additional studies indicated that CA1P induced microtubule depolymerization-mediated AKT inactivation, which resulted in GSK-3β activation, Wnt/β-Catenin pathway inhibition, and Mcl-1 down-regulation...
September 28, 2016: Cancer Letters
Guido Carpino, Valerio Nobili, Anastasia Renzi, Cristiano De Stefanis, Laura Stronati, Antonio Franchitto, Anna Alisi, Paolo Onori, Rita De Vito, Gianfranco Alpini, Eugenio Gaudio
Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric non-alcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included...
2016: PloS One
Wen-Chien Huang, Mei-Lin Chan, Ming-Jen Chen, Tung-Hu Tsai, Yu-Jen Chen
Tumor-associated macrophages (TAMs) polarized to the M2 phenotype play key roles in tumor progression in different cancer types, including lung cancer. MUC1 expression in various types of cancer is an indicator of poorer prognosis. Elevated MUC1 expression has been reported in inflammatory lung macrophages and is associated with lung cancer development. Here, we investigated the role of M2-polarized TAMs (M2-TAMs) in the generation of lung cancer stem cells (LCSCs) and tested pterostilbene, a small-molecule agent that modulates MUC1 expression in lung cancer cells, with the goal of subverting the microenvironment toward a favorable anti-tumor impact...
June 4, 2016: Oncotarget
Ming Li, Hu Chen, Luxi Chen, Yaosheng Chen, Xiaohong Liu, Delin Mo
MicroRNAs (miRNAs) are endogenous small non-coding RNAs which modulate gene expression at the post-transcriptional level by either translational inhibition or mRNA degradation. MicroRNAs play important roles in both innate and adaptive immune response, including TLR-triggered immune response. In this study, we found that the expression of miR-709 was up-regulated in primary macrophage and RAW264.7 cells during the stimulation of LPS. Overexpression of miR-709 in RAW264.7 cells led to reduced production and gene expression of inflammatory cytokines (IL-6, TNF-α, IL-1β) during activation by LPS, whereas knockdown of miR-709 had completely opposite effects...
May 24, 2016: International Immunopharmacology
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