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https://www.readbyqxmd.com/read/29052866/runx-mediated-growth-arrest-and-senescence-are-attenuated-by-diverse-mechanisms-in-cells-expressing-runx1-fusion-oncoproteins
#1
Gail Anderson, Nancy Mackay, Kathryn Gilroy, Jodie Hay, Gillian Borland, Alma McDonald, Margaret Bell, Siti Ayuni Hassanudin, Ewan Cameron, James C Neil, Anna Kilbey
RUNX gene over-expression inhibits growth of primary cells but transforms cells with tumor suppressor defects, consistent with reported associations with tumor progression. In contrast, chromosomal translocations involving RUNX1 are detectable in utero, suggesting an initiating role in leukemias. How do cells expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression? Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable to induce senescence-like growth arrest (SLGA) in primary fibroblasts while potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29052317/defective-ciliogenesis-in-inpp5e-related-joubert-syndrome
#2
Isabel Hardee, Ariane Soldatos, Mariska Davids, Thierry Vilboux, Camilo Toro, Karen L David, Carlos R Ferreira, Michele Nehrebecky, Joseph Snow, Audrey Thurm, Theo Heller, Ellen F Macnamara, Meral Gunay-Aygun, Wadih M Zein, William A Gahl, May Christine V Malicdan
Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate 5-phosphatase E, which is important in the development and stability of the primary cilium...
October 20, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29050985/bromodomain-protein-brd4-promotes-cell-proliferation-in-skin-squamous-cell-carcinoma
#3
Tie Xiang, Jin-Yu Bai, Cang She, Dao-Jiang Yu, Xiao-Zhong Zhou, Tian-Lan Zhao
The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Furthermore, BRD4 knockdown (by targeted shRNAs) or knockout (by CRISPR/Cas9) largely inhibited A431 cell proliferation...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29049722/a-ppar-gamma-agonist-rosiglitazone-suppresses-fibrotic-response-in-human-pterygium-fibroblasts-by-modulating-the-p38-mapk-pathway
#4
Selikem Abla Nuwormegbe, Joon Hyung Sohn, Sun Woong Kim
Purpose: Fibroblast activation may play an important role in pterygium progression. Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods: Profibrotic activation was induced by TGF-β1 in primary cultured human pterygium fibroblasts and the effect of rosiglitazone treatment on α-smooth muscle actin (α-SMA), and extra cellular matrix proteins synthesis was detected by western blotting, real-time PCR, immunostaining, and flow cytometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29048426/fgf1-protects-neuroblastoma-sh-sy5y-cells-from-p53-dependent-apoptosis-through-an-intracrine-pathway-regulated-by-fgf1-phosphorylation
#5
Caroline Pirou, Fatemeh Montazer-Torbati, Nadège Jah, Elisabeth Delmas, Christelle Lasbleiz, Bernard Mignotte, Flore Renaud
Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29047077/adventitial-fibroblast-nox4-expression-and-ros-signaling-in-pulmonary-arterial-hypertension
#6
Scott A Barman, David Fulton
Pulmonary arterial hypertension (PAH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4), a constitutively active enzyme, has been associated with oxygen sensing, vasomotor control, cellular proliferation, differentiation, migration, apoptosis, senescence, fibrosis, and angiogenesis. Further, elevated expression of Nox4 has been reported in a number of cardiovascular diseases, including atherosclerosis, hypertension, cardiac failure, ischemic stroke, and PAH...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046460/myeloid-dendritic-cells-repress-human-cytomegalovirus-gene-expression-and-spread-by-releasing-interferon-unrelated-soluble-antiviral-factors
#7
Bahram Kasmapour, Tobias Kubsch, Ulfert Rand, Britta Eiz-Vesper, Martin Messerle, Florian W R Vondran, Bettina Wiegmann, Axel Haverich, Luka Cicin-Sain
Cytomegalovirus (CMV) is a beta-herpesvirus that latently infects most adult humans worldwide and is a major cause of morbidity and mortality in immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in precursors of myeloid-lineage, leukocytes and monocytes, which give raise to macrophages and dendritic cells. We report here that human monocyte derived DCs (mo-DC) suppress HCMV infection in coculture with infected fibroblasts target cells in an effector-to-target-ratio dependent manner. Intriguingly, optimal activation of mo-DC was achieved in coculture conditions, not by their direct infection with HCMV, implying that mo-DC may recognize unique molecular patterns on, or within, infected fibroblasts...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29045803/chitosan-based-trilayer-scaffold-for-multitissue-periodontal-regeneration
#8
E M Varoni, S Vijayakumar, E Canciani, A Cochis, L De Nardo, G Lodi, L Rimondini, M Cerruti
Periodontal regeneration is still a challenge for periodontists and tissue engineers, as it requires the simultaneous restoration of different tissues-namely, cementum, gingiva, bone, and periodontal ligament (PDL). Here, we synthetized a chitosan (CH)-based trilayer porous scaffold to achieve periodontal regeneration driven by multitissue simultaneous healing. We produced 2 porous compartments for bone and gingiva regeneration by cross-linking with genipin either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze-drying the resulting scaffolds...
October 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29045028/biological-effects-of-er-yag-laser-irradiation-on-the-proliferation-of-primary-human-gingival-fibroblasts
#9
Sophannary Kong, Akira Aoki, Kengo Iwasaki, Koji Mizutani, Sayaka Katagiri, Tomonari Suda, Shizuko Ichinose, Mayumi Ogita, Verica Pavlic, Yuichi Izumi
We investigated the biological effects of Er:YAG laser (2,940-nm; DELight(®) , HOYA ConBio, USA) irradiation at fluences of 3.6, 4.2, 4.9, 6.3, 8.1, or 9.7 J cm(-2) at 20 or 30 Hz for 20 or 30 s on primary human gingival fibroblasts (HGFs). Irradiation at 6.3 J cm(-2) promoted maximal cell proliferation, determined by WST-8 assay and crystal violet staining, but was accompanied by lactate dehydrogenase release, on day 3 post-irradiation. Elevation of ATP level, Ki67 staining, and cyclin-A2 mRNA expression confirmed that Er:YAG affected the cell cycle and increased the number of proliferating cells...
October 17, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/29041931/reprogramming-of-stromal-fibroblasts-by-snai2-contributes-to-tumor-desmoplasia-and-ovarian-cancer-progression
#10
Zongyuan Yang, Xin Yang, Sen Xu, Ping Jin, Xiaoting Li, Xiao Wei, Dan Liu, Kecheng Huang, Sixiang Long, Ya Wang, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Ding Ma, Qinglei Gao
BACKGROUND: Molecular profiling in ovarian cancer (OC) revealed that the desmoplasia subtype presented the poorest prognosis, highlighting the contribution of stromal fibroblasts in tumor progression. This study aimed to investigate the molecular characteristics of SNAI2 driving the transcriptional reprogramming of fibroblasts within tumors. METHODS: SNAI2 expression was evaluated in microdissected profiles of various cancers and in various molecular subtypes of OC...
October 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29041897/small-molecule-modulation-of-splicing-factor-expression-is-associated-with-rescue-from-cellular-senescence
#11
Eva Latorre, Vishal C Birar, Angela N Sheerin, J Charles C Jeynes, Amy Hooper, Helen R Dawe, David Melzer, Lynne S Cox, Richard G A Faragher, Elizabeth L Ostler, Lorna W Harries
BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence...
October 17, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29040558/constitutively-active-fgfr3-disrupts-primary-cilium-length-and-ift20-trafficking-in-various-chondrocyte-models-of-achondroplasia
#12
Ludovic Martin, Nabil Kaci, Valentin Estibals, Nicolas Goudin, Meriem Garfa-Traore, Catherine Benoist-Lasselin, Emilie Dambroise, Laurence Legeai-Mallet
FGFR3 (fibroblast growth factor receptor 3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively-active FGFR3 perturbed PC length and the sorting and trafficking of IFT20 to the PC...
October 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29038245/mitochondrial-calcium-dysregulation-contributes-to-dendrite-degeneration-mediated-by-pd-lbd-associated-lrrk2-mutants
#13
Manish Verma, Jason Callio, P Anthony Otero, Israel Sekler, Zachary P Wills
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs prior to the well-characterized phenotype of dendritic shortening...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29037838/expression-and-epigenetic-regulation-of-cystatin-b-in-lung-cancer-and-colorectal-cancer
#14
Yunxia Ma, Yuan Chen, Iver Petersen
AIMS: Dysregulated expression of cystatin B (CSTB) has been implicated in various cancers. The aims of this study were to analyze the CSTB expression and investigate the epigenetic regulation of CSTB in lung and colon cancer cell lines, and also evaluate the clinical outcome of CSTB in primary lung and colorectal tumors. METHODS: CSTB expression in lung and colon cancer cell lines was analyzed by real-time RT-PCR and western blotting. Epigenetic regulation of CSTB was examined by demethylation, deacetylation tests and bisulfite sequencing (BS)...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29034471/lipid-signaling-affects-primary-fibroblast-collective-migration-and-anchorage-in-response-to-stiffness-and-microtopography
#15
Michael A Mkrtschjan, Snehal B Gaikwad, Kevin J Kappenman, Christopher Solís, Sagar Dommaraju, Long Le, Tejal A Desai, Brenda Russell
Cell migration is regulated by several mechanotransduction pathways, which consist of sensing and converting mechanical microenvironmental cues to internal biochemical cellular signals, such as protein phosphorylation and lipid signaling. While there has been significant progress in understanding protein changes in the context of mechanotransduction, lipid signaling is more difficult to investigate. In this study, physical cues of stiffness (10 kPa, 100 kPa, 400 kPa, and glass), and microrod or micropost topography were manipulated in order to reprogram primary fibroblasts and assess the effects of lipid signaling on the actin cytoskeleton...
October 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29032370/an-immunofluorescence-assay-for-extracellular-matrix-components-highlights-the-role-of-epithelial-cells-in-producing-a-stable-fibrillar-extracellular-matrix
#16
Omar S Qureshi, Hélène Bon, Breda Twomey, Gill Holdsworth, Kirsty Ford, Marianne Bergin, Linghong Huang, Mariusz Muzylak, Louise J Healy, Vanessa Hurdowar, Timothy S Johnson
Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM) in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29030810/an-in-vitro-model-of-cellular-quiescence-in-primary-human-dermal-fibroblasts
#17
Mithun Mitra, Linda D Ho, Hilary A Coller
Cellular quiescence is a reversible mode of cell cycle exit that allows cells and organisms to withstand unfavorable stress conditions. The factors that underlie the entry, exit, and maintenance of the quiescent state are crucial for understanding normal tissue development and function as well as pathological conditions such as chronic wound healing and cancer. In vitro models of quiescence have been used to understand the factors that contribute to quiescence under well-controlled experimental conditions. Here, we describe an in vitro model of quiescence that is based on neonatal human dermal fibroblasts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030113/proteomic-analyses-of-signalling-complexes-associated-with-receptor-tyrosine-kinase-identify-novel-members-of-fibroblast-growth-factor-receptor-3-interactome
#18
Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3)...
October 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29029400/rat-embryonic-fibroblasts-immortalized-by-mrps18-2-protein-are-target-for-nk-cells
#19
Muhammad Mushtaq, Pradeepa N Pangigadde, Suhas Darekar, Erik Dissen, Elena Kashuba
Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response. In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation in vitro. However, unlike stem cells, 18IM cells do not develop tumors in vivo, in SCID mice...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029099/biomarkers-of-mineral-and-bone-metabolism-and-20-year-risk-for-hospitalization-with-infection-the-aric-study
#20
Junichi Ishigami, Bernard G Jaar, Casey M Rebholz, Morgan E Grams, Erin D Michos, Myles Wolf, Csaba P Kovesdy, Shinichi Uchida, Josef Coresh, Pamela L Lutsey, Kunihiro Matsushita
Context: Mineral and bone disorders (MBD) may be relevant in the etiology of infection. Objective: To determine whether MBD biomarkers were associated with incidence of hospitalization with infection. We also assessed the cross-sectional association between levels of MBD biomarkers and kidney function. Design: Setting, Participants: Community-based cohort study using 11,218 participants with estimated glomerular filtration rate (eGFR) ≥30 ml/min/1...
September 27, 2017: Journal of Clinical Endocrinology and Metabolism
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