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https://www.readbyqxmd.com/read/27907201/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-promotes-hepatic-stellate-cells-migration-via-canonical-nf-%C3%AE%C2%BAb-mmp9-pathway
#1
Mingcui Xu, Feng Zhang, Aixiu Wang, Chen Wang, Yu Cao, Ming Zhang, Mingming Zhang, Min Su, Xiaoping Zou, Guifang Xu, Yuzheng Zhuge
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65...
2016: PloS One
https://www.readbyqxmd.com/read/27862656/matrix-metalloproteinase-12-mmp-12-deficiency-attenuates-experimental-crescentic-anti-gbm-glomerulonephritis
#2
Abu P Abraham, Frank Y Ma, William R Mulley, David J Nikolic-Paterson, Greg H Tesch
AIM: MMP-12 (macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. METHODS: Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild type C57BL/6 J (WT) controls, which were killed 12 days after injection of anti-GBM serum...
November 8, 2016: Nephrology
https://www.readbyqxmd.com/read/27811142/loss-of-epithelial-gq-and-g11-signaling-inhibits-tgf%C3%AE-production-but-promotes-il-33-mediated-macrophage-polarization-and-emphysema
#3
Alison E John, Michael R Wilson, Anthony Habgood, Joanne Porte, Amanda L Tatler, Anastasios Stavrou, Gino Miele, Lisa Jolly, Alan J Knox, Masao Takata, Stefan Offermanns, R Gisli Jenkins
Heterotrimeric guanine nucleotide-binding protein (G protein) signaling links hundreds of G protein-coupled receptors with four G protein signaling pathways. Two of these, one mediated by Gq and G11 (Gq/11) and the other by G12 and G13 (G12/13), are implicated in the force-dependent activation of transforming growth factor-β (TGFβ) in lung epithelial cells. Reduced TGFβ activation in alveolar cells leads to emphysema, whereas enhanced TGFβ activation promotes acute lung injury and idiopathic pulmonary fibrosis...
October 25, 2016: Science Signaling
https://www.readbyqxmd.com/read/27807143/hif-kdm3a-mmp12-regulatory-circuit-ensures-trophoblast-plasticity-and-placental-adaptations-to-hypoxia
#4
Damayanti Chakraborty, Wei Cui, Gracy X Rosario, Regan L Scott, Pramod Dhakal, Stephen J Renaud, Makoto Tachibana, M A Karim Rumi, Clifford W Mason, Adam J Krieg, Michael J Soares
The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. Hypoxia plays an instructive role in influencing trophoblast cell differentiation and regulating placental organization. Key downstream hypoxia-activated events were delineated using rat TS cells and tested in vivo, using trophoblast-specific lentiviral gene delivery and genome editing...
November 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27798868/gene-expression-analysis-identifies-specific-patterns-of-dysregulated-molecular-pathways-and-genetic-subgroups-of-human-hepatocellular-carcinoma
#5
Holger G Hass, Ulrich Vogel, Michael Scheurlen, Jürgen Jobst
BACKGROUND: Hepatocellular carcinoma comprises of a group of heterogeneous tumors of different etiologies. The multistep process of liver carcinogenesis involves various genetic and phenotypic alterations. The molecular pathways and driver mutations involved are still under investigation. MATERIALS AND METHODS: DNA micorarray technology was used to identify differentially expressed genes between human hepatocarcinoma and non-tumorous liver tissues to establish a unique specific gene-expression profile independent of the underlying liver disease...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27796860/genetic-risk-factors-for-ischemic-and-hemorrhagic-stroke
#6
REVIEW
Ganesh Chauhan, Stéphanie Debette
Understanding the genetic risk factors for stroke is an essential step to decipher the underlying mechanisms, facilitate the identification of novel therapeutic targets, and optimize the design of prevention strategies. A very small proportion of strokes are attributable to monogenic conditions, the vast majority being multifactorial, with multiple genetic and environmental risk factors of small effect size. Genome-wide association studies and large international consortia have been instrumental in finding genetic risk factors for stroke...
December 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27742835/the-torc1-activated-proteins-p70s6k-and-grb10-regulate-il-4-signaling-and-m2-macrophage-polarization-by-modulating-phosphorylation-of-insulin-receptor-substrate-2
#7
Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate-2 (IRS-2) in macrophages. We hypothesized that negative regulation of IRS-2 activity after IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (Tyr(P)) and serine phosphorylation (Ser(P)) of IRS-2 after IL-4 stimulation...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27699251/cell-type-deconvolution-with-immune-pathways-identifies-gene-networks-of-host-defense-and-immunopathology-in-leprosy
#8
Megan S Inkeles, Rosane M B Teles, Delila Pouldar, Priscila R Andrade, Cressida A Madigan, David Lopez, Mike Ambrose, Mahdad Noursadeghi, Euzenir N Sarno, Thomas H Rea, Maria T Ochoa, M Luisa Iruela-Arispe, William R Swindell, Tom H M Ottenhoff, Annemieke Geluk, Barry R Bloom, Matteo Pellegrini, Robert L Modlin
Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution...
September 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/27699230/a-cord-blood-monocyte-derived-cell-therapy-product-accelerates-brain-remyelination
#9
Arjun Saha, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, Aruni Gunaratne, Tracy Gentry, Jesse Troy, Glenn K Matsushima, Joanne Kurtzberg, Andrew E Balber
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14(+) monocytes. We compared the ability of freshly isolated CB CD14(+) monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγ(null) mice following cuprizone feeding-mediated demyelination...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27698806/matrix-metalloproteinase-expression-and-molecular-interaction-network-analysis-in-gastric-cancer
#10
Jianting Xu, Changyong E, Yongfang Yao, Shuangchun Ren, Guoqing Wang, Haofan Jin
Gastric cancer (GC) is one of the most common types of cancer of the digestive tract. Invasion of tumor cells into surrounding tissue and metastasis are among the most significant checkpoints in tumor progression. It is known that matrix metalloproteinases (MMPs) are involved in these processes; however, knowledge of their molecular interaction networks is still limited. Investigation of these networks could provide a more comprehensive picture of the function of MMPs in tumorigenesis. Furthermore, it could be used to develop new approaches to targeted anticancer therapy...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27530235/serum-pharmacodynamic-biomarkers-for-chronic-corticosteroid-treatment-of-children
#11
Yetrib Hathout, Laurie S Conklin, Haeri Seol, Heather Gordish-Dressman, Kristy J Brown, Lauren P Morgenroth, Kanneboyina Nagaraju, Christopher R Heier, Jesse M Damsker, John N van den Anker, Erik Henricson, Paula R Clemens, Jean K Mah, Craig McDonald, Eric P Hoffman
Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27501402/a-possible-interaction-between-periostin-and-cd163-skin-resident-macrophages-in-pemphigus-vulgaris-and-bullous-pemphigoid
#12
Taku Fujimura, Aya Kakizaki, Sadanori Furudate, Setsuya Aiba
Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are autoimmune blistering diseases, and substantial numbers of CD163(+) tissue-associated macrophages (TAMs) are detected in both diseases. PV and BP possess different subsets of helper T cells, suggesting that the cytokine profiles of PV and BP might be different. The purpose of the present study is to investigate the microenvironment of lesional skin and serum of PV and BP patients, focusing on the immunomodulatory factors related to TAMs, such as periostin (POSTN), chemokines, cytokines and matrix metalloproteinases...
August 8, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27473120/acacia-honey-accelerates-in-vitro-corneal-ulcer-wound-healing-model
#13
Norzana Abd Ghafar, Choy Ker-Woon, Chua Kien Hui, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah
BACKGROUND: The study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts. METHODS: Stromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0...
2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27456476/neutrophil-elastase-and-matrix-metalloproteinase-12-in-cystic-fibrosis-lung-disease
#14
REVIEW
Claudius J Wagner, Carsten Schultz, Marcus A Mall
Chronic lung disease remains the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Recent studies in young children with CF diagnosed by newborn screening identified neutrophil elastase (NE), a major product released from neutrophils in inflamed airways, as a key risk factor for the onset and early progression of CF lung disease. However, the understanding of how NE and potentially other proteases contribute to the complex in vivo pathogenesis of CF lung disease remains limited. In this review, we summarize recent progress in this area based on studies in βENaC-overexpressing (βENaC-Tg) mice featuring CF-like lung disease and novel protease-specific Förster resonance energy transfer (FRET) sensors for localization and quantification of protease activity in the lung...
December 2016: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/27448665/cigarette-smoke-causes-acute-airway-disease-and-exacerbates-chronic-obstructive-lung-disease-in-neonatal-mice
#15
Jie Jia, Thomas M Conlon, Carolina Ballester Lopez, Michael Seimetz, Mariola Bednorz, Zhe Zhou-Suckow, Norbert Weissmann, Oliver Eickelberg, Marcus A Mall, Ali Önder Yildirim
Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27431388/serum-mmp7-mmp10-and-mmp12-level-as-negative-prognostic-markers-in-colon-cancer-patients
#16
Fee Klupp, Lena Neumann, Christoph Kahlert, Johannes Diers, Niels Halama, Clemens Franz, Thomas Schmidt, Moritz Koch, Juergen Weitz, Martin Schneider, Alexis Ulrich
BACKGROUND: Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers. METHODS: Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27391467/differential-matrix-metalloprotease-mmp-expression-profiles-found-in-aged-gingiva
#17
Suhee Kim, Sun Hee Ahn, Jin-Sil Lee, Ji-Eun Song, Sung-Hyun Cho, Seunggon Jung, Seon-Kyu Kim, Seok-Ho Kim, Kwang-Pyo Lee, Ki-Sun Kwon, Tae-Hoon Lee
The periodontium undergoes age-related cellular and clinical changes, but the involved genes are not yet known. Here, we investigated age-related genetic changes in gingiva at the transcriptomic level. Genes that were differentially expressed between young and old human gingiva were identified by RNA sequencing and verified by real-time PCR. A total of 1939 mRNA transcripts showed significantly differential expression between young and old gingival tissues. Matrix metalloprotease (MMP) regulation was the top pathway involved in gingival aging...
2016: PloS One
https://www.readbyqxmd.com/read/27385318/identification-of-matrix-metalloproteinase-12-as-a-candidate-molecule-for-prevention-and-treatment-of-cardiometabolic-disease
#18
Melina Amor, Veronica Moreno-Viedma, Alisina Sarabi, Nicole G Grün, Bianca Itariu, Lukas Leitner, Irene Steiner, Martin Bilban, Keiichi Kodama, Atul J Butte, Guenther Staffler, Maximilian Zeyda, Thomas M Stulnig
Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively...
June 30, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27375023/tnf%C3%AE-activated-mesenchymal-stromal-cells-promote-breast-cancer-metastasis-by-recruiting-cxcr2-neutrophils
#19
P F Yu, Y Huang, Y Y Han, L Y Lin, W H Sun, A B Rabson, Y Wang, Y F Shi
Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. Our previous work demonstrated that tumor necrosis factor α (TNFα)-activated MSCs significantly promoted tumor growth. However, the role of TNFα-treated MSCs in tumor metastasis remains elusive. Employing a lung metastasis model of murine breast cancer, we found that TNFα-activated MSCs strikingly enhanced tumor metastasis compared with normal MSCs. We analyzed the chemokine profiles and found that the expression of CCL5, CCR2 and CXCR2 ligands were enhanced in TNFα-activated MSCs...
July 4, 2016: Oncogene
https://www.readbyqxmd.com/read/27373742/plasma-matrix-metalloproteinases-in-stroke-patients-during-intensive-rehabilitation-therapy
#20
Feifei Ma, Susana Rodriguez, Xavi Buxo, Anna Morancho, Iolanda Riba-Llena, Ana Carrera, Alejandro Bustamante, Dolors Giralt, Joan Montaner, Carmen Martinez, Immaculada Bori, Anna Rosell
OBJECTIVE: To study plasma levels of matrix metalloproteinases (MMPs) as potential markers of recovery during intensive rehabilitation therapy (IRT) after stroke. DESIGN: Prospective and descriptive 3-months follow-up study. SETTING: Rehabilitation unit and research center. PARTICIPANTS: Patients with first-ever ischemic strokes (n=15) enrolled to IRT (≥3 hours per day/5 days per week) and healthy volunteers serving as non-ischemic controls (n=15)...
June 30, 2016: Archives of Physical Medicine and Rehabilitation
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