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lysyl oxidase

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https://www.readbyqxmd.com/read/28638462/reorganized-collagen-in-the-tumor-microenvironment-of-gastric-cancer-and-its-association-with-prognosis
#1
Zhi-Hua Zhou, Cheng-Dong Ji, Hua-Liang Xiao, Hai-Bin Zhao, You-Hong Cui, Xiu-Wu Bian
Collagen components in the tumor microenvironment substantially influence cancer pathogenesis and progression. Nevertheless, in gastric cancer, collagen status and its prognostic role remain unclear. Using picrosirius red staining and immunohistochemistry, we found that collagen deposition was significantly increased in gastric cancer when compared with non-neoplastic tissues, and in cancer stroma, more immature collagen components were present, suggesting a qualitative change. Furthermore, the morphology of collagen fibers could be weakly, moderately or strongly changed in gastric cancer; when weakly or moderately changed, they appeared similar to normal collagen fibers, except for a higher linearization and density; when strongly changed, they were thicker and less eosinophilic, sharply differently from their normal counterparts...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28624448/identification-of-functional-hypoxia-inducible-factor-response-elements-in-the-human-lysyl-oxidase-gene-promoter
#2
Victoria Wang, David A Davis, Robert Yarchoan
Human lysyl oxidase (LOX) is a hypoxia-responsive gene whose product catalyzes collagen crosslinking and is thought to be important in cancer metastasis and osteoarthritis. We previously demonstrated that LOX was upregulated by hypoxia inducible factor 2 (HIF-2) more strongly than hypoxia inducible 1 (HIF-1). We further investigated the response of the LOX gene and LOX promoter to HIFs. LOX mRNA, measured by real time reverse transcriptase-PCR, was strongly up-regulated (almost 40-fold), by transfection of HEK-293T cells with a plasmid encoding the HIF-2α subunit of HIF-2, but only three-fold by a plasmid encoding HIF-1α...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28624291/vascular-lysyl-oxidase-over-expression-alters-extracellular-matrix-structure-and-induces-oxidative-stress
#3
Saray Varona, Ana B García-Redondo, Jose Martínez-González, Mercedes Salaices, Ana M Briones, Cristina Rodríguez
INTRODUCTION: Lysyl oxidase (LOX) participates in the assembly of collagen and elastin fibres. The impact of vascular LOX over-expression on extracellular matrix (ECM) structure and its contribution to oxidative stress has been analysed. METHODS: Studies were conducted on mice over-expressing LOX (Tg), specifically in smooth muscle cells (VSMC). Gene expression was assessed by real-time PCR analysis. Sirius Red staining, H2O2 production and NADPH oxidase activity were analysed in different vascular beds...
June 14, 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28623328/platelet-rich-plasma-induces-post-natal-maturation-of-immature-articular-cartilage-and-correlates-with-loxl1-activation
#4
Yadan Zhang, Ben J Morgan, Rachel Smith, Christopher R Fellows, Catherine Thornton, Martyn Snow, Lewis W Francis, Ilyas M Khan
Platelet-rich plasma (PRP) is used to stimulate the repair of acute and chronic cartilage damage even though there is no definitive evidence of how this is achieved. Chondrocytes in injured and diseased situations frequently re-express phenotypic biomarkers of immature cartilage so tissue maturation is a potential pathway for restoration of normal structure and function. We used an in vitro model of growth factor-induced maturation to perform a comparative study in order to determine whether PRP can also induce this specific form of remodeling that is characterised by increased cellular proliferation and tissue stiffness...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#5
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28598820/role-of-loxl2-in-the-epithelial-mesenchymal-transition-and-colorectal-cancer-metastasis
#6
Pil-Gu Park, Su Ji Jo, Min Jung Kim, Hyun Jeong Kim, Ji Hae Lee, Cheol Keun Park, Hyunki Kim, Kang Young Lee, Hoguen Kim, Jeon Han Park, Seung Myung Dong, Jae Myun Lee
Colorectal cancer (CRC) is one of the most dangerous types of malignant tumors, and cancer metastasis is a major factor in the failure of CRC therapy. Recently, LOXL2 (lysyl oxidase-like 2) has been shown to represent a regulator of epithelial-mesenchymal transition (EMT) in different cancer types. However, LOXL2 has not been reported to be involved in CRC metastasis. In this study, we demonstrated that LOXL2 expression is strongly correlated with the rate of CRC metastasis, it participates in the regulation of EMT-related molecule expression in CRC cells in vitro, and it is involved in migratory potential alterations...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592436/bladder-fibrosis-during-outlet-obstruction-is-triggered-through-the-nlrp3-inflammasome-and-the-production-of-il-1%C3%AE
#7
Francis Monty Hughes, Stephanie J Sexton, Huixia Jin, Vihasa Govada, J Todd Purves
Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1β produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into 5 groups: 1) control, 2) sham, 3) BOO + Vehicle, 4) BOO + the NLRP3 inhibitor glyburide or 5) BOO + the IL-1β receptor antagonist anakinra...
June 7, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28592432/up-regulation-of-lysyl-oxidase-and-adhesion-to-collagen-of-human-megakaryocytes-and-platelets-in-primary-myelofibrosis
#8
Vittorio Abbonante, Vipul Chitalia, Vittorio Rosti, Orly Leiva, Shinobu Matsuura, Alessandra Balduini, Katya Ravid
No abstract text is available yet for this article.
June 7, 2017: Blood
https://www.readbyqxmd.com/read/28574510/rip4-inhibits-stat3-signaling-to-sustain-lung-adenocarcinoma-differentiation
#9
Jawahar Kopparam, Johanna Chiffelle, Paolo Angelino, Alessandra Piersigilli, Nadine Zangger, Mauro Delorenzi, Etienne Meylan
Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28570270/molecular-imaging-of-oxidized-collagen-quantifies-pulmonary-and-hepatic-fibrogenesis
#10
Howard H Chen, Philip A Waghorn, Lan Wei, Luis F Tapias, Daniel T Schu Hle, Nicholas J Rotile, Chloe M Jones, Richard J Looby, Gaofeng Zhao, Justin M Elliott, Clemens K Probst, Mari Mino-Kenudson, Gregory Y Lauwers, Andrew M Tager, Kenneth K Tanabe, Michael Lanuti, Bryan C Fuchs, Peter Caravan
Fibrosis results from the dysregulation of tissue repair mechanisms affecting major organ systems, leading to chronic extracellular matrix buildup, and progressive, often fatal, organ failure. Current diagnosis relies on invasive biopsies. Noninvasive methods today cannot distinguish actively progressive fibrogenesis from stable scar, and thus are insensitive for monitoring disease activity or therapeutic responses. Collagen oxidation is a universal signature of active fibrogenesis that precedes collagen crosslinking...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28568134/lysyl-oxidase-mediated-vegf-induced-differentiation-and-angiogenesis-in-human-dental-pulp-cells
#11
W J Bae, J K Yi, J Park, S K Kang, J H Jang, E C Kim
AIM: To investigate the effects of recombinant human vascular endothelial growth factor (rhVEGF) on odontoblastic differentiation, in vitro angiogenesis, and expression and activity of lysyl oxidase (LOX) in human dental pulp cells (HDPCs), compared with rhFGF-2. To identify the underlying molecular mechanisms, the study focused on whether LOX was responsible for the actions of rhVEGF. METHODOLOGY: rhVEGF was constructed using the pBAD-HisA plasmid in Escherichia coli...
June 1, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28559441/apmap-interacts-with-lysyl-oxidase-like-proteins-and-disruption-of-apmap-leads-to-beneficial-visceral-adipose-tissue-expansion
#12
Ariane R Pessentheiner, Katharina Huber, Helmut J Pelzmann, Andreas Prokesch, Franz P W Radner, Heimo Wolinski, Josefine Lindroos-Christensen, Gerald Hoefler, Thomas Rülicke, Ruth Birner-Gruenberger, Martin Bilban, Juliane G Bogner-Strauss
Adipocyte plasma membrane-associated protein (APMAP) has been described as an adipogenic factor in 3T3-L1 cells with unknown biochemical function; we therefore aimed to investigate the physiologic function of APMAP in vivo We generated Apmap-knockout mice and challenged them with an obesogenic diet to investigate their metabolic phenotype. We identified a novel truncated adipocyte-specific isoform of APMAP in mice that is produced by alternative transcription. Mice lacking the full-length APMAP protein, the only isoform that is expressed in humans, have an improved metabolic phenotype upon diet-induced obesity, indicated by enhanced insulin sensitivity, preserved glucose tolerance, increased respiratory exchange ratio, decreased inflammatory marker gene expression, and reduced adipocyte size...
May 30, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28553358/inhibition-of-lysyl-oxidases-impairs-migration-and-angiogenic-properties-of-tumor-associated-pericytes
#13
Aline Lopes Ribeiro, Carolini Kaid, Patrícia B G Silva, Beatriz A Cortez, Oswaldo Keith Okamoto
Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28550176/mechanical-behavior-and-matrisome-gene-expression-in-aneurysm-prone-thoracic-aorta-of-newborn-lysyl-oxidase-knockout-mice
#14
Marius Catalin Staiculescu, Jungsil Kim, Robert P Mecham, Jessica Wagenseil
Mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysm and dissection (TAAD). Mice that do not express Lox (Lox(-/-)) die soon after birth and have 60% and 40% reductions in elastin- and collagen-specific crosslinks, respectively. LOX inactivation could also change the expression of secreted factors, structural matrix, and matrix-associated proteins that constitute the aortic matrisome. We hypothesize that the absence of Lox will change the mechanical behavior of the aortic wall due to reduced elastin and collagen crosslinking and alter the expression levels of matrisome and smooth muscle cell (SMC) genes in a vascular location-specific manner...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28538980/downregulation-of-lysyl-oxidase-protects-retinal-endothelial-cells-from-high-glucose-induced-apoptosis
#15
Dongjoon Kim, Robert P Mecham, Philip C Trackman, Sayon Roy
Purpose: To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#16
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28522596/lysyl-oxidase-overexpression-accelerates-cardiac-remodeling-and-aggravates-angiotensin-ii-induced-hypertrophy
#17
María Galán, Saray Varona, Anna Guadall, Mar Orriols, Miquel Navas, Silvia Aguiló, Alicia de Diego, María A Navarro, David García-Dorado, Antonio Rodríguez-Sinovas, José Martínez-González, Cristina Rodriguez
Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic mouse model with a strong cardiac expression of human LOX (TgLOX). TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522400/impact-of-lysyl-oxidase-g473a-polymorphism-on-diabetic-foot-ulcers
#18
Sivakamasundari Pichu, Jayalalitha Sathiyamoorthy, Selvaraj Vimalraj, Vijay Viswanathan, Suvro Chatterjee
Lysyl oxidase (LOX) is an extra-cellular matrix-modifying enzyme that has been linked to cell proliferation, metastasis, angiogenesis and wound healing. This study was designed to examine the association of LOX gene polymorphism G473A, G>A, (rs1800449) located in exon 1 of the LOX gene in diabetic subjects with and without diabetic foot ulcers (DFU) and its impact of expression on DFU. Genotypic analysis of 906 samples showed a significant increase in the presence of 'A' allele in type 2 diabetes mellitus (T2DM) and DFU when compared to that of control subjects...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28508064/fibulin-4-is-essential-for-maintaining-arterial-wall-integrity-in-conduit-but-not-muscular-arteries
#19
Carmen M Halabi, Thomas J Broekelmann, Michelle Lin, Vivian S Lee, Mon-Li Chu, Robert P Mecham
Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4(E57K/E57K) mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28503365/genetics-diagnosis-and-monitoring-of-pseudoexfoliation-glaucoma
#20
Niraj Nathan, Rachel W Kuchtey
Recent studies have shed new light on the genetic factors underlying pseudoexfoliation syndrome, growing our understanding of the role of the lysyl oxidase-like 1 (LOXL1) gene and its various polymorphisms as well as identifying new genetic associations. Recent years have brought new insight on how these genetic factors interact with other factors, including environmental, to confer risk to individuals and populations worldwide. All of these findings may hold importance to the screening, diagnosis, and monitoring of pseudoexfoliation and may also help lead to the identification of novel therapeutic targets...
December 2016: Current Ophthalmology Reports
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