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Dörthe Masemann, Rafael Leite Dantas, Siarhei Sitnik, Tanja Schied, Carolin Nordhoff, Stephan Ludwig, Viktor Wixler
FHL2 is a multifunctional adaptor protein with fine-tuning adjustment properties. It acts as a regulator of signaling cascades but also as a cofactor of transcription and controls several anti-inflammatory immune responses. Recently, we described FHL2 as a novel regulator of influenza A virus propagation. We have shown that in vitro FHL2 restricts viral replication by accelerating the IRF-3-dependent transcription of the Ifnb1 gene. In this work, we unraveled an ambiguous role of FHL2 during influenza A virus infection in vivo...
February 17, 2018: American Journal of Pathology
Chiara Messina, Marco Zecca, Franca Fagioli, Attilio Rovelli, Stefano Giardino, Pietro Merli, Fulvio Porta, Maurizio Aricò, Elena Sieni, Giuseppe Basso, Mimmo Ripaldi, Claudio Favre, Marta Pillon, Antonio Marzollo, Marco Rabusin, Simone Cesaro, Mattia Algeri, Maurizio Caniglia, Paolo Di Bartolomeo, Ottavio Ziino, Francesco Saglio, Arcangelo Prete, Franco Locatelli
We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%) or other defined disorders known to cause HLH (15%); in the remaining patients, no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%) and an HLA-partially matched family donor for 11 children (10%)...
February 1, 2018: Biology of Blood and Marrow Transplantation
Natalia Nunez, Aurélie Derré-Bobillot, Stéphane Gaubert, Jean-Marie Herry, Julien Deschamps, Yu Wei, Thomas Baranek, Mustapha Si-Tahar, Romain Briandet, Pascale Serror, Cristel Archambaud
Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E. faecalis also known as a virulence factor. ElrA was previously shown to prevent adhesion to macrophages...
January 29, 2018: Scientific Reports
C I Lorda-Diez, J A Montero, C Sanchez-Fernandez, J A Garcia-Porrero, J Chimal-Monroy, J M Hurle
FHL2 is a multifunctional scaffolding protein of well-known function regulating cell signaling cascades and gene transcription in cancer tissues. However, its function in embryonic systems is poorly characterized. Here, we show that Fhl2 is involved in the differentiation of connective tissues of developing limb autopod. We show that Fhl2 exhibits spatially restricted and temporally dynamic expression around the tendons of developing digits, interphalangeal joint capsules, and fibrous peridigital tissue. Immunolabeling analysis of the skeletal progenitors identified a predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated with focal adhesions and actin cytoskeleton...
January 12, 2018: Journal of Tissue Engineering and Regenerative Medicine
Jingci Chen, Alison M Nagle, Yu-Fen Wang, David N Boone, Adrian V Lee
Breast cancer development and progression is influenced by insulin-like growth factor 1 (IGF1R) and insulin receptor (InsR) signaling that drive cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and InsR form IGF1R/InsR hybrid receptors (HybR) consisting of one molecule of IGF1R and one molecule of InsR. The specific signaling and functions of HybR are largely unknown as HybR is activated by both IGF1 and insulin, and no cellular system expresses HybR in the absence of holo-IGF1R or holo-InsR...
January 12, 2018: Journal of Biological Chemistry
Lili Sun, Shuye Yu, Hui Xu, Yanwen Zheng, Juntang Lin, Meiyan Wu, Jide Wang, Aidong Wang, Qing Lan, Frank Furnari, Webster Cavenee, Benjamin Purow, Ming Li
Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family, which plays a critical role in tumorigenesis. We previously reported that FHL2 is upregulated and plays an oncogenic role in glioblastoma (GBM), the most common and aggressive brain tumor. GBM is also marked by amplification of the epidermal growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the most common and functionally significant. Here we report that FHL2 physically interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells...
January 11, 2018: Oncogene
Chia-Wei Chang, Chih-Chia Chang, Kuo-Chiang Hsia, Su-Yi Tsai
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Mutations in the FHL2 (Four and a half LIM domains protein 2) gene are associated with cardiomyopathy in patients. Here, we generated two homozygous knockout lines using CRISPR/Cas9-mediated ablation in a human embryonic stem cell (hESC) WA09 line. These knockout lines exhibit a normal karyotype without expressing FHL2 protein, while maintaining pluripotency and differentiation properties. These isogenic mutation lines will be provided as a disease model for cardiomyopathy studies and drug screening...
December 23, 2017: Stem Cell Research
Ting Cai, Danqin Sun, Ying Duan, Yumei Qiu, Chunsun Dai, Junwei Yang, Weichun He
β-Catenin signalling plays an important role in regulating tubular epithelial-to-mesenchymal transition (EMT), an indispensable programme for driving renal fibrosis. As an adapter protein, four and a half LIM domain protein 2 (FHL2) acts as a coregulator of β-catenin in several other cell types. To determine whether FHL2 affects β-catenin signalling and thus is involved in tubular EMT, we examined its expression and function in the process of TGF-β1-induced EMT. FHL2 mRNA and protein were induced by TGF-β1 in rat tubular epithelial cells (NRK-52E), an effect that intracellular Smad signalling was required...
March 2018: Journal of Cellular and Molecular Medicine
Erdinç Dursun, Duygu Gezen-Ak
Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins...
2017: PloS One
Sarah Walachowski, Guillaume Tabouret, Marion Fabre, Gilles Foucras
β-Glucans (BGs) are glucose polymers present in the fungal cell wall (CW) and, as such, are recognized by innate immune cells as microbial-associated pattern through Dectin-1 receptor. Recent studies have highlighted the ability of the pathogenic yeast Candida albicans or its CW-derived β(1,3) (1,6)-glucans to increase human monocytes cytokine secretion upon secondary stimulation, a phenomenon now referred as immune training. This ability of monocytes programming confers BGs an undeniable immunotherapeutic potential...
2017: Frontiers in Immunology
Xiaoping Yi, Hongyan Zai, Xueying Long, Xiaoyi Wang, Wenzheng Li, Yixiong Li
Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associated with tumor metastasis...
October 2017: Oncology Letters
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...
October 2017: Journal of Leukocyte Biology
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
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...
September 15, 2017: Journal of Biological Chemistry
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
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
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
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
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
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
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