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Wnt inflammation

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https://www.readbyqxmd.com/read/29339085/wnt5a-mediates-chronic-post-thoracotomy-pain-by-regulating-non-canonical-pathways-nerve-regeneration-and-inflammation-in-rats
#1
Afang Zhu, Le Shen, Li Xu, Weiyun Chen, Yuguang Huang
As well-characterized ligands involved in neurogenesis, Wnts are emerging as promising targets in pain pathogenesis. Our previous pilot study showed that intrathecal inhibition of Wnt5a, but not Wnts, relieves chronic post-thoracotomy pain (CPTP) in rats. In the present study, we aimed to further explore the regulatory mechanism of Wnt5a in CPTP development. Increased protein levels of Wnt5a, transmembrane receptor Ror2, and activated non-canonical Wnt pathway members were found in the thoracic dorsal root ganglions from postoperative day (POD) 7 to POD 21...
January 12, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29330435/beta-catenin-cleavage-enhances-transcriptional-activation
#2
Tatiana Goretsky, Emily M Bradford, Qing Ye, Olivia F Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C Keller, Preetika Sinh, Josep M Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A Barrett
Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327327/identifying-potentially-common-genes-between-dyslipidemia-and-osteoporosis-using-novel-analytical-approaches
#3
Xu Lin, Cheng Peng, Jonathan Greenbaum, Zhang-Fang Li, Ke-Hao Wu, Zeng-Xin Ao, Tong Zhang, Jie Shen, Hong-Wen Deng
Dyslipidemia (DL) is closely related to osteoporosis (OP), while the exact common genetic mechanisms are still largely unknown. We proposed to use novel genetic analysis methods with pleiotropic information to identify potentially novel and/or common genes for the potential shared pathogenesis associated with OP and/or DL. We assessed the pleiotropy between plasma lipid (PL) and femoral neck bone mineral density (FNK BMD). We jointly applied the conditional false discovery rate (cFDR) method and the genetic analysis incorporating pleiotropy and annotation (GPA) method to the summary statistics provided by genome-wide association studies (GWASs) of FNK BMD (n = 49,988) and PL (n = 188,577) to identify potentially novel and/or common genes for BMD/PL...
January 11, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29323748/the-gain-of-function-mutation-e76k-in-shp2-promotes-cac-tumorigenesis-and-induces-emt-via-the-wnt-%C3%AE-catenin-signaling-pathway
#4
Qian Zhang, Rongrong Zhao, Chuling Fan, Xinyi Wang, Youzhi Xu, Yakun Liu, Siying Wang
SHP2 is encoded by the protein tyrosine phosphatase 11 (Ptpn11) gene. Several gain-of-function (GOF) mutations in Ptpn11 have been identified in human hematopoietic malignancies and solid tumors. In addition, the mutation rate for SHP2 is the highest for colorectal cancer (CRC) among solid tumors. The E76K GOF mutation is the most common and active SHP2 mutation; however, the pathogenic effects and function of this mutation in CRC tumor progression have not been well characterized. The Wnt/β-catenin (CTNNB1) signaling pathway is crucial for CRC, and excessive activation of this pathway has been observed in several tumors...
January 11, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29317436/the-diabetes-gene-and-wnt-pathway-effector-tcf7l2-regulates-adipocyte-development-and-function
#5
Xi Chen, Ayala Iriscilla, Chris Shannon, Marcel Fourcaudot, Nikhil K Acharya, Christopher P Jenkinson, Sami Heikkinen, Luke Norton
The gene encoding for transcription factor 7-like 2 (TCF7L2) is the strongest type 2 diabetes (T2DM) candidate gene discovered to date. The TCF7L2 protein is a key transcriptional effector of the Wnt/β-catenin signaling pathway, which is an important developmental pathway that negatively regulates adipogenesis. However, the precise role that TCF7L2 plays in the development and function of adipocytes remains largely unknown. Using a combination of in vitro approaches, we first show that TCF7L2 protein is increased during adipogenesis in 3T3-L1 cells and primary adipocyte stem cells (ASC), and that TCF7L2 expression is required for the regulation of Wnt signaling during adipogenesis...
January 9, 2018: Diabetes
https://www.readbyqxmd.com/read/29317265/wound-regeneration-deficit-in-rats-correlates-with-low-morphogenetic-potential-and-distinct-transcriptome-profile-of-epidermis
#6
Christian F Guerrero-Juarez, Aliaksandr A Astrowski, Rabi Murad, Christina T Dang, Vera O Shatrova, Aksana Astrowskaja, Chae Ho Lim, Raul Ramos, Xiaojie Wang, Yuchen Liu, Hye-Lim Lee, Kim T Pham, Tsai-Ching Hsi, Ji Won Oh, Daniel Crocker, Ali Mortazavi, Mayumi Ito, Maksim V Plikus
Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats, across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs respectively, yet prominent inter-species differences exist...
January 6, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29317052/iron-therapy-as-treatment-of-anemia-a-potentially-detrimental-and-hazardous-strategy-in-colorectal-cancer-patients
#7
M J Wilson, J J Harlaar, J Jeekel, M Schipperus, J J Zwaginga
In colorectal cancer patients, iron therapy, and especially intravenous iron therapy, is increasingly used to treat anemia and reduce the use of blood transfusions. However, iron has also been shown to be an essential nutrient for rapidly proliferating tissues and cells. In this respect, anemia of inflammation, characterized by limited duodenal iron uptake and sequestration of iron into the reticuloendothelial system, might be regarded as a potentially effective defense strategy of the human body against tumor growth...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29305909/targeting-oncogenic-transcription-factors-by-polyphenols-a-novel-approach-for-cancer-therapy
#8
REVIEW
Chitra Rajagopal, Manendra Babu Lankadasari, Jesil Mathew Aranjani, K B Harikumar
Inflammation is one of the major causative factor of cancer and chronic inflammation is involved in all the major steps of cancer initiation, progression metastasis and drug resistance. The molecular mechanism of inflammation driven cancer is the complex interplay between oncogenic and tumor suppressive transcription factors which include FOXM1, NF-kB, STAT3,Wnt/β- Catenin, HIF-1α,NRF2, androgen and estrogen receptors. Several products derived from natural sources modulate the expression and activity of multiple transcription factors in various tumor models as evident from studies conducted in cell lines, pre-clinical models and clinical samples...
January 3, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29298515/vitex-rotundifolia-fruit-suppresses-the-proliferation-of-human-colorectal-cancer-cells-through-down-regulation-of-cyclin-d1-and-cdk4-via-proteasomal-dependent-degradation-and-transcriptional-inhibition
#9
Hun Min Song, Gwang Hun Park, Su Bin Park, Hyun-Seok Kim, Ho-Jun Son, Yurry Um, Jin Boo Jeong
Viticis Fructus (VF) as the dried fruit from Vitex rotundifolia L. used as a traditional medicine for treating inflammation, headache, migraine, chronic bronchitis, eye pain, and gastrointestinal infections has been reported to have antiproliferative effects against various cancer cells, including breast, lung and colorectal cancer cells. However, the molecular mechanisms by which VF mediates the inhibitory effect of the proliferation of cancer cells have not been elucidated in detail. In this study, we investigated the molecular mechanism of VF on the down-regulation of cyclin D1 and CDK4 level associated with cancer cell proliferation...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29296769/wnt-ligands-contribute-to-the-immune-response-during-septic-shock-and-amplify-endotoxemia-driven-inflammation-in-mice
#10
Marcela Gatica-Andrades, Dimitrios Vagenas, Jessica Kling, Tam T K Nguyen, Helen Benham, Ranjeny Thomas, Heinrich Körner, Bala Venkatesh, Jeremy Cohen, Antje Blumenthal
Improved understanding of the molecular mechanisms underlying dysregulated inflammatory responses in severe infection and septic shock is urgently needed to improve patient management and identify new therapeutic opportunities. The WNT signaling pathway has been implicated as a novel constituent of the immune response to infection, but its contribution to the host response in septic shock is unknown. Although individual WNT proteins have been ascribed pro- or anti-inflammatory functions, their concerted contributions to inflammation in vivo remain to be clearly defined...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284609/dkk3-dickkopf-3-alters-atherosclerotic-plaque-phenotype-involving-vascular-progenitor-and-fibroblast-differentiation-into-smooth-muscle-cells
#11
Eirini Karamariti, Chungang Zhai, Baoqi Yu, Qiao Lei, Zhihong Wang, Claire M F Potter, Mei Mei Wong, Russell M L Simpson, Zhongyi Zhang, Xiaocong Wang, Ivan Del Barco Barrantes, Christof Niehrs, Deling Kong, Qiang Zhao, Yun Zhang, Yanhua Hu, Cheng Zhang, Qingbo Xu
OBJECTIVES: DKK3 (dickkopf 3), a 36-kD secreted glycoprotein, has been shown to be involved in the differentiation of partially reprogrammed cells and embryonic stem cells to smooth muscle cells (SMCs), but little is known about its involvement in vascular disease. This study aims to assess the effects of DKK3 on atherosclerotic plaque composition. APPROACH AND RESULTS: In the present study, we used a murine model of atherosclerosis (ApoE-/-) in conjunction with DKK3-/- and performed tandem stenosis of the carotid artery to evaluate atherosclerotic plaque development...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29275462/cancer-immunotherapy-targets-based-on-understanding-the-t-cell-inflamed-versus-non-t-cell-inflamed-tumor-microenvironment
#12
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29258883/cartilage-regeneration-and-ageing-targeting-cellular-plasticity-in-osteoarthritis
#13
REVIEW
Marta Varela-Eirin, Jesus Loureiro, Eduardo Fonseca, Silvia Corrochano, Jose R Caeiro, Manuel Collado, Maria D Mayan
Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes...
December 16, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29258711/mechanisms-of-aortic-stenosis
#14
REVIEW
Hirokuni Akahori, Takeshi Tsujino, Tohru Masuyama, Masaharu Ishihara
The pathobiology of degenerative aortic valve stenosis (AS) is complex and involves multiple features such as fibrosis, inflammation, oxidative stress, angiogenesis, hemorrhage, and osteogenic differentiation. We summarize the mechanism of valve calcification and angiogenesis which is necessary for calcifying processes. A promising therapeutic target is nuclear factor (NF)-κB which activates bone morphogenetic protein (BMP)2 via interleukin-6. BMP2 activates Wnt signaling via msh homeobox 2 causing osteogenic differentiation...
December 16, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29246763/wnt-%C3%AE-catenin-pathway-promotes-acute-lung-injury-induced-by-lps-through-driving-the-th17-response-in-mice
#15
Li Cheng, Yan Zhao, Di Qi, Wen Li, Daoxin Wang
T helper cell 17 (Th17), one type of CD4+ T cell, plays an important role in regulating the acute lung injury (ALI) inflammatory response. Recent studies showed that Wnt/β-catenin pathway could modulate the differentiation and the function of CD4+ T cell. However, whether Wnt/β-catenin could regulate the differentiation and function of Th17 in the development and progress of ALI induced by lipopolysaccharide (LPS) is still unknown. To test this, we used dickkopf1 (Dkk-1) to block the Wnt/β-catenin pathway and LiCl to activate the Wnt/β-catenin pathway by instillation to the murine model of ALI...
December 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29233185/phosphoproteomics-reveals-network-rewiring-to-a-pro-adhesion-state-in-annexin-1-deficient-mammary-epithelial-cells
#16
Asfa Alli-Shaik, Sheena Wee, Lina H K Lim, Jayantha Gunaratne
BACKGROUND: Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells...
December 12, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29229927/activation-of-non-canonical-wnt-signaling-in-human-visceral-adipose-tissue-contributes-to-local-and-systemic-inflammation
#17
María A Zuriaga, José J Fuster, Melissa G Farb, Susan MacLauchlan, Rosa Bretón-Romero, Shakun Karki, Donald T Hess, Caroline M Apovian, Naomi M Hamburg, Noyan Gokce, Kenneth Walsh
The accumulation of visceral adiposity is strongly associated with systemic inflammation and increased cardiometabolic risk. WNT5A, a non-canonical WNT ligand, has been shown to promote adipose tissue inflammation and insulin resistance in animal studies. Among other non-canonical pathways, WNT5A activates planar cell polarity (PCP) signaling. The current study investigated the potential contribution of non-canonical WNT5A/PCP signaling to visceral adipose tissue (VAT) inflammation and associated metabolic dysfunction in individuals with obesity...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217752/mapping-the-distribution-of-stem-progenitor-cells-across-the-middle-ear-during-homeostasis-and-inflammation
#18
Abigail S Tucker, Carlene J Dyer, Juan M Fons Romero, Tathyane H N Teshima, Jennifer C Fuchs, Hannah Thompson
The middle ear epithelium is derived from neural crest and endoderm, which line distinct regions of the middle ear cavity. Here we investigate the distribution of putative stem cell markers in the middle ear combined with an analysis of the location of label retaining cells (LRCs) to create a map of the middle ear mucosa. We show that proliferating cells and LRCs were associated with specific regions of the ear epithelium, concentrated in the hypotympanum at the base of the auditory bulla and around the ear drum...
December 7, 2017: Development
https://www.readbyqxmd.com/read/29217140/inhibition-of-canonical-wnt-signaling-pathway-by-%C3%AE-catenin-cbp-inhibitor-icg-001-ameliorates-liver-fibrosis-in-vivo-through-suppression-of-stromal-cxcl12
#19
Büsra Öztürk Akcora, Gert Storm, Ruchi Bansal
Quiescent hepatic stellate cells (HSCs), in response to liver injury, undergo characteristic morphological transformation into proliferative, contractile and ECM-producing myofibroblasts. In this study, we investigated the implication of canonical Wnt signaling pathway in HSCs and liver fibrogenesis. Canonical Wnt signaling pathway activation and inhibition using β-catenin/CBP inhibitor ICG001 was examined in-vitro in TGFβ-activated 3T3, LX2, primary human HSCs, and in-vivo in CCl4-induced acute liver injury mouse model...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29215066/pharmacological-inhibition-of-rev-erb-stimulates-differentiation-inhibits-turnover-and-reduces-fibrosis-in-dystrophic-muscle
#20
Ryan D Welch, Cyrielle Billon, Aurore-Cecile Valfort, Thomas P Burris, Colin A Flaveny
Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function...
December 7, 2017: Scientific Reports
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