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https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#1
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28725932/dna-methylation-in-elovl2-and-c1orf132-correctly-predicted-chronological-age-of-individuals-from-three-disease-groups
#2
M Spólnicka, E Pośpiech, B Pepłońska, R Zbieć-Piekarska, Ż Makowska, A Pięta, J Karłowska-Pik, B Ziemkiewicz, M Wężyk, P Gasperowicz, T Bednarczuk, M Barcikowska, C Żekanowski, R Płoski, Wojciech Branicki
Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions...
July 19, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28717008/the-cardiac-z-disc-protein-cefip-regulates-cardiomyocyte-hypertrophy-by-modulating-calcineurin-signaling
#3
Franziska Dierck, Christian Kuhn, Claudia Rohr, Susanne Hille, Julia Braune, Samuel Sossalla, Sibylle Molt, Peter F M van der Ven, Dieter O Fürst, Norbert Frey
The z-disc is a structural component at the lateral borders of the sarcomere and is important for mechanical stability and contractility of both cardiac and skeletal muscles. Of note, the sarcomeric z-disc also represents a nodal point in cardiomyocyte function and signaling. Mutations of numerous z-disc proteins are associated with cardiomyopathies and muscle diseases. To identify additional z-disc proteins that might contribute to cardiac disease, we employed an in silico screen for cardiac-enriched cDNAs...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28714941/autophagy-induced-fhl2-upregulation-promotes-il-6-production-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-mouse-aortic-endothelial-cells-after-exposure-to-pm2-5
#4
Wen-Rong Xia, Wenliang Fu, Qin Wang, Xiaoming Zhu, Wei-Wei Xing, Min Wang, Dong-Qun Xu, Dong-Gang Xu
Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with cardiovascular morbidity and mortality, which share the common feature of PM2.5-induced vascular inflammation; however, the underlying mechanisms of how PM2.5 triggers increased inflammatory response in vascular endothelial cells are not well understood. After treating mouse aortic endothelial cells (MAECs) with different concentrations of PM2.5, we assessed interleukin (IL)-6 and four and a half LIM domains 2 (FHL2) expression in cell supernatant by enzyme-linked immunosorbent assay and Western blot, respectively, as well as activation of nuclear factor (NF)-κB and immune-response signaling pathways...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28677795/ctbp2-is-associated-with-angiogenesis-and-regulates-the-apoptosis-of-prostate-cancer-cells
#5
Qiang Xuan, Xiaoge Zhong, Weidong Li, Zengnan Mo, Yuanjie Huang, Yanling Hu
Angiogenesis is associated with prostate cancer (PCa) development and progression. Aberrant expression of C-terminal binding protein (CtBP)2 has been observed in PCa, but whether its change in expression plays a significant role in angiogenesis has not been completely characterized. we attempted to integrate and analyze the genome-wide association study (GWAS) of follicle stimulating hormone receptor (FSHR) and CtBP2, the Cancer Genome Atlas (TCGA) data and CtBP2 binding data in CistromeMap (18) to explore the mechanism of CtBP2 in PCa, and performed pathway enrichment analysis...
June 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676674/the-enterococcus-faecalis-virulence-factor-elra-interacts-with-the-human-four-and-a-half-lim-domains-protein-2
#6
Alexandre Jamet, Rozenn Dervyn, Nicolas Lapaque, Francesca Bugli, Naima G Perez-Cortez, Hervé M Blottière, Jean-Claude Twizere, Maurizio Sanguinetti, Brunella Posteraro, Pascale Serror, Emmanuelle Maguin
The commensal bacterium Enterococcus faecalis is a common cause of nosocomial infections worldwide. The increasing prevalence of multi-antibiotic resistant E. faecalis strains reinforces this public health concern. Despite numerous studies highlighting several pathology-related genetic traits, the molecular mechanisms of E. faecalis virulence remain poorly understood. In this work, we studied 23 bacterial proteins that could be considered as virulence factors or involved in the Enterococcus interaction with the host...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28662101/specific-gene-expression-signatures-induced-by-the-multiple-oncogenic-alterations-that-occur-within-the-pten-pi3k-akt-pathway-in-lung-cancer
#7
Carmela De Marco, Carmelo Laudanna, Nicola Rinaldo, Duarte Mendes Oliveira, Maria Ravo, Alessandro Weisz, Michele Ceccarelli, Elvira Caira, Antonia Rizzuto, Pietro Zoppoli, Donatella Malanga, Giuseppe Viglietto
Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN...
2017: PloS One
https://www.readbyqxmd.com/read/28511095/independent-validation-of-dna-based-approaches-for-age-prediction-in-blood
#8
Sohee Cho, Sang-Eun Jung, Sae Rom Hong, Eun Hee Lee, Ji Hyun Lee, Soong Deok Lee, Hwan Young Lee
Numerous molecular biomarkers have been proposed as predictors of chronological age. Among them, T-cell specific DNA rearrangement and DNA methylation markers have been introduced as forensic age predictors in blood because of their high prediction accuracy. These markers appear highly promising, but for better application to forensic casework sample analysis the proposed markers and genotyping methods must be tested further. In the current study, signal-joint T-cell receptor excision circles (sjTRECs) and DNA methylation markers located in the ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 genes were reanalyzed in 100 Korean blood samples to test their associations with chronological age, using the same analysis platform used in previous reports...
July 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28499412/genome-wide-dna-methylation-analysis-reveals-hypomethylation-in-the-low-cpg-promoter-regions-in-lymphoblastoid-cell-lines
#9
Itsuki Taniguchi, Chihiro Iwaya, Keizo Ohnaka, Hiroki Shibata, Ken Yamamoto
BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases...
May 12, 2017: Human Genomics
https://www.readbyqxmd.com/read/28489964/specific-activation-of-plekhg2-induced-serum-response-element-dependent-gene-transcription-by-four-and-a-half-lim-domains-fhl-1-but-not-fhl2-or-fhl3
#10
Masashi Nishikawa, Katsuya Sato, Shun Nakano, Hisashi Yamakawa, Takahiro Nagase, Hiroshi Ueda
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#11
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402264/fhl2-interacts-with-iaspp-and-impacts-the-biological-functions-of-leukemia-cells
#12
Wenting Lu, Tengteng Yu, Shuang Liu, Saisai Li, Shouyun Li, Jia Liu, Yingxi Xu, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Jianxiang Wang, Min Wang
iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP. FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted with each other and co-localized in both nucleus and cytoplasm...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28349819/adam-17-fhl2-colocalisation-suggests-interaction-and-role-of-these-proteins-in-colorectal-cancer
#13
Laurine Verset, Joke Tommelein, Christine Decaestecker, Elly De Vlieghere, Marc Bracke, Isabelle Salmon, Olivier De Wever, Pieter Demetter
FHL2 is a multifunctional scaffolding protein; its expression is associated with poor prognosis in colorectal cancer. ADAM-17 is a metalloprotease implicated in ectodomain shedding. FHL2 regulates ADAM-17 plasma membrane localisation, and FHL2 deficiency leads to decreased activity of ADAM-17 in mouse macrophages. Presence and relationship of the ADAM-17/FHL2 complex with colorectal cancer progression is unknown. We studied FHL2 and ADAM-17 expression in several colon cancer cell lines by immunocytochemistry and western blot...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28320530/single-cell-rna-sequence-analysis-of-mouse-glomerular-mesangial-cells-uncovers-mesangial-cell-essential-genes
#14
Yuqiu Lu, Yuting Ye, Qianqian Yang, Shaolin Shi
Mesangial cells are essential for the structure and function of glomeruli, but the mechanisms underlying these roles are not well understood. Here, we performed a single-cell RNA-sequence (RNA-seq) analysis of mouse mesangial cells using the Fluidigm C1 platform. We found that gene expression in individual mesangial cells was tremendously heterogeneous, with mean correlation coefficients of 0.20, and most mesangial genes were actually expressed in only a portion of mesangial cells and are therefore presumably dispensable...
March 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28243234/fhl2-regulates-natural-killer-cell-development-and-activation-during-streptococcus-pneumoniae-infection
#15
Thomas Baranek, Eric Morello, Alexandre Valayer, Rose-France Aimar, Déborah Bréa, Clemence Henry, Anne-Gaelle Besnard, Emilie Dalloneau, Antoine Guillon, Pierre-François Dequin, Emilie Narni-Mancinelli, Eric Vivier, Fabrice Laurent, Yu Wei, Christophe Paget, Mustapha Si-Tahar
Recent in silico studies suggested that the transcription cofactor LIM-only protein FHL2 is a major transcriptional regulator of mouse natural killer (NK) cells. However, the expression and role of FHL2 in NK cell biology are unknown. Here, we confirm that FHL2 is expressed in both mouse and human NK cells. Using FHL2(-/-) mice, we found that FHL2 controls NK cell development in the bone marrow and maturation in peripheral organs. To evaluate the importance of FHL2 in NK cell activation, FHL2(-/-) mice were infected with Streptococcus pneumoniae...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223370/lim-only-protein-fhl2-is-a-negative-regulator-of-transforming-growth-factor-%C3%AE-1-expression
#16
Jennifer Dahan, Florence Levillayer, Tian Xia, Yann Nouët, Catherine Werts, Martine Fanton d'Andon, Minou Adib-Conquy, Anne-Marie Cassard-Doulcier, Varun Khanna, Ju Chen, Thierry Tordjmann, Marie-Annick Buendia, Grégory Jouvion, Yu Wei
Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FHL2 is a transcriptional cofactor that plays the role of coactivator or corepressor, depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2(-/-) cells than in wild-type (WT) cells in a reporter assay...
May 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27892920/foxk1-interaction-with-fhl2-promotes-proliferation-invasion-and-metastasis-in-colorectal-cancer
#17
M Wu, J Wang, W Tang, X Zhan, Y Li, Y Peng, X Huang, Y Bai, J Zhao, A Li, C Chen, Y Chen, H Peng, Y Ren, G Li, S Liu, J Wang
The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT-PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays...
November 28, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27742790/matrix-mechanics-controls-fhl2-movement-to-the-nucleus-to-activate-p21-expression
#18
Naotaka Nakazawa, Aneesh R Sathe, G V Shivashankar, Michael P Sheetz
Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27672102/systemic-age-associated-dna-hypermethylation-of-elovl2-gene-in-vivo-and-in-vitro-evidences-of-a-cell-replication-process
#19
Maria Giulia Bacalini, Joris Deelen, Chiara Pirazzini, Marco De Cecco, Cristina Giuliani, Catia Lanzarini, Francesco Ravaioli, Elena Marasco, Diana van Heemst, H Eka D Suchiman, Roderick Slieker, Enrico Giampieri, Rina Recchioni, Fiorella Mercheselli, Stefano Salvioli, Giovanni Vitale, Fabiola Olivieri, Annemieke M W Spijkerman, Martijn E T Dollé, John M Sedivy, Gastone Castellani, Claudio Franceschi, Pieternella E Slagboom, Paolo Garagnani
Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2 We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age...
September 26, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27622035/missense-mutations-in-the-perforin-prf1-gene-as-a-cause-of-hereditary-cancer-predisposition
#20
Mohammed S Chaudhry, Kimberly C Gilmour, Imran G House, Mark Layton, Nicki Panoskaltsis, Mamta Sohal, Joseph A Trapani, Ilia Voskoboinik
Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies...
July 2016: Oncoimmunology
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