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lysyl oxidase

Alison Gartland, Janine T Erler, Thomas R Cox
Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour...
September 2016: Journal of Bone Oncology
Mahmut Asfuroglu, Busranur Cavdarli, Ozlem G Koz, Ahmet A Yarangumeli, Emine Y Ozdemir
PURPOSE: To investigate the genetic association of lysyl oxidase-like 1 (LOXL1) gene polymorphisms in patients with pseudoexfoliation (PEX) syndrome and PEX glaucoma of Turkish descent. METHODS: Three LOXL1 single nucleotide polymorphisms (SNPs) (rs1048661, rs3825942, and rs2165241) were analyzed in 109 Turkish patients (44 patients with PEX syndrome, 65 patients with PEX glaucoma) and 47 healthy subjects. RESULTS: "A" allele of SNP rs3825942 was underrepresented in control group compared with the glaucoma [odds ratio (OR)=4...
October 6, 2016: Journal of Glaucoma
Caroline Reynaud, Laura Ferreras, Paola Di Mauro, Casina Kan, Martine Croset, Edith Bonnelye, Floriane Pez, Clémence Thomas, Géraldine Aimont, Antoine E Karnoub, Marie Brevet, Philippe Clezardin
Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase whose primary function is to drive collagen crosslinking and extracellular matrix stiffness. LOX in colorectal cancer (CRC) synergizes with hypoxia-inducible factor-1 (HIF-1alpha to promote tumor progression. Here we investigated whether LOX/HIF1 endows CRC cells with full competence for aggressive colonization in bone. We show that a high LOX expression in primary tumors from CRC patients was associated with poor clinical outcome, irrespective of HIF-1...
October 14, 2016: Cancer Research
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Laura Pascual, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Ane Iturbide, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene...
October 13, 2016: FEBS Journal
Natasha Pahuja, Nimisha R Kumar, Rushad Shroff, Rohit Shetty, Rudy M M A Nuijts, Anuprita Ghosh, Abhijit Sinha-Roy, Shyam S Chaurasia, Rajiv R Mohan, Arkasubhra Ghosh
Purpose: In this study, we elucidated the differential expression of a set of local molecular factors in ectatic cone area of the cornea to uncover a functional cause for focal corneal weakening characteristic of the keratoconus (KC) disease. Methods: All human corneal samples were collected after approval of Institutional Ethics Committee and informed consent. Keratoconus patients were classified based on clinical parameters, topographical features, and structural deformity...
October 1, 2016: Investigative Ophthalmology & Visual Science
Yueshui Zhao, Xue Gu, Ningyan Zhang, Mikhail G Kolonin, Zhiqiang An, Kai Sun
Endotrophin is a cleavage product of collagen 6 (Col6) in adipose tissue (AT). Previously, we demonstrated that endotrophin serves as a costimulator to trigger fibrosis and inflammation within the unhealthy AT milieu. However, how endotrophin affects lipid storage and breakdown in AT and how different cell types in AT respond to endotrophin stimulation remain unknown. In the current study, by using a doxycycline (Dox)-inducible mouse model, we observed significant upregulation of adipogenic genes in the WAT of endotrophin Tg mice...
October 11, 2016: American Journal of Physiology. Endocrinology and Metabolism
Zakaria Ezzoukhry, Elodie Henriet, Léo Piquet, Kevin Boyé, Paulette Bioulac-Sage, Charles Balabaud, Gabrielle Couchy, Jessica Zucman-Rossi, Violaine Moreau, Frédéric Saltel
Transforming growth factor-β1 (TGF-β1) is an important player in chronic liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC) development. TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels. TGF-β1 was described to enhance production of type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2 (LOXL2). In addition, TGF-β1 and type I collagen are potent inducers of invadosomes. Indeed, type I collagen fibers induce the formation of active linear invadosomes through the discoidin domain receptor 1 (DDR1)...
October 4, 2016: European Journal of Cell Biology
D H Peng, C Ungewiss, P Tong, L A Byers, J Wang, J R Canales, P A Villalobos, N Uraoka, B Mino, C Behrens, I I Wistuba, R I Han, C A Wanna, M Fahrenholtz, K J Grande-Allen, C J Creighton, D L Gibbons
Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis...
October 3, 2016: Oncogene
Arif Tasleem Jan, Eun Ju Lee, Inho Choi
Fibromodulin (FMOD) is a small leucine-rich proteoglycan that plays roles in a series of biological and pathophysiological processes. The interaction between FMOD and lysyl oxidase (LOX; collagen cross-linking enzyme) helps regulate extracellular matrix composition, and thereby, provides a permissive environment for regulating cellular turnover. FMOD has been mostly studied in the context of matrix component assembly, but during recent years its association with muscle development, cell reprogramming, and the angiogenic program have demonstrated its activities well beyond extracellular matrix maintenance...
September 28, 2016: International Journal of Biochemistry & Cell Biology
Heather N Hutson, Taylor Marohl, Matthew Anderson, Kevin Eliceiri, Paul Campagnola, Kristyn S Masters
Disorganization of the valve extracellular matrix (ECM) is a hallmark of calcific aortic valve disease (CAVD). However, while microarchitectural features of the ECM can strongly influence the biological and mechanical behavior of tissues, little is known about the ECM microarchitecture in CAVD. In this work, we apply advanced imaging techniques to quantify spatially heterogeneous changes in collagen microarchitecture in CAVD. Human aortic valves were obtained from individuals between 50 and 75 years old with no evidence of valvular disease (healthy) and individuals who underwent valve replacement surgery due to severe stenosis (diseased)...
2016: PloS One
Cheri L Lamb, Giovan N Cholico, Daniel E Perkins, Michael T Fewkes, Julia Thom Oxford, Trevor J Lujan, Erica E Morrill, Kristen A Mitchell
The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover...
2016: BioMed Research International
Archita Das, Varadarajan Sudhahar, Gin-Fu Chen, Ha Won Kim, Seock-Won Youn, Lydia Finney, Stefan Vogt, Jay Yang, Junghun Kweon, Bayasgalan Surenkhuu, Masuko Ushio-Fukai, Tohru Fukai
Copper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1(-/-) mice...
September 26, 2016: Scientific Reports
Mitsuru Saito, Keishi Marumo
Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory disease associated with an increase of fracture risk. Bone strength is determined by bone mass and quality.Bone quality is thought to encompass the structural and material properties of bone. Bone collagen crosslinking plays important roles in bone strength. The quantitative and qualitative deterioration of lysyl oxidase control and non enzymatic cross-links(advanced glycation end products, AGEs, pentosidine)of collagen in patients with osteoporotic femoral neck fracture and diabetes, and COPD might be affected by increased oxidative stress and glycation...
2016: Clinical Calcium
Dick Wågsäter, Emina Vorkapic, Caroline M W van Stijn, Jason Kim, Aldons J Lusis, Per Eriksson, Rajendra K Tangirala
Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR(-/-)) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP)...
2016: Scientific Reports
Jian Zhang, Ziyi Liu, Tingting Zhang, Zhuchun Lin, Zhenzu Li, Aizhen Zhang, Xiaoyang Sun, Jiangang Gao
Lysyl oxidase-like 3 (LOXL3), a human disease gene candidate, is a member of the lysyl oxidase (LOX) family and is indispensable for mouse palatogenesis and vertebral column development. Our previous study showed that the loss of LOXL3 resulted in a severe cleft palate and spinal deformity. In this study, we investigated a possible role for LOXL3 in mouse embryonic lung development. LOXL3-deficient mice displayed reduced lung volumes and weights, diminished saccular spaces, and deformed and smaller thoracic cavities...
2016: Scientific Reports
Masayuki Tsukasaki, Koki Hamada, Kazuo Okamoto, Kazuki Nagashima, Asuka Terashima, Noriko Komatsu, Stephanie J Win, Tadashi Okamura, Takeshi Nitta, Hisataka Yasuda, Josef M Penninger, Hiroshi Takayanagi
Osteoclasts are the exclusive bone-resorbing cells that have a central role in bone homeostasis as well as bone destruction in cancer and autoimmune disease. Both mouse and human genetic studies have clearly proven that receptor activator of NF-κB ligand (RANKL; encoded by the Tnfsf11 gene) and its receptor RANK are essential for osteoclastogenesis. Although there have been several reports on RANKL-independent osteoclastogenesis, previous studies have never provided in vivo evidence showing RANKL can be substituted by other molecules using RANKL- or RANK-deficient genetic backgrounds...
September 8, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Tonia C Rothuizen, Raymond Kemp, Jacques M G J Duijs, Hetty C De Boer, Roel Bijkerk, Eric P Van der Veer, Lorenzo Moroni, Anton Jan Van Zonneveld, Anthony S Weiss, Ton J Rabelink, Joris I Rotmans
BACKGROUND: Elastin, critical for its structural and regulatory functions, is a missing link in vascular tissue engineering. Several elastin-inducting compounds have previously been reported, but their relative efficiency in promoting elastogenesis by adult arterial and venous vascular smooth muscle cells (VSMCs) and fibroblasts, four main vascular and elastogenic cells, has not been described. In addition to elasto-inductive substances, microRNA-29a was recently established as a potent post-transcriptional inhibitor of elastogenesis...
September 7, 2016: Tissue Engineering. Part C, Methods
Aurélie Comptour, Marion Rouzaire, Corinne Belville, Nicolas Bonnin, Estelle Daniel, Frédéric Chiambaretta, Loïc Blanchon, Vincent Sapin
Vitamin A and its active forms (retinoic acids/RAs) are known to have pro-healing properties, but their mechanisms of action are still poorly understood. This work aimed to identify the cellular and molecular processes by which atRA (all-trans RA) improves wound healing, using an in vivo model of mouse corneal alkali burns and an in vitro cellular human corneal epithelial injury model. Regulation by atRA has been studied on most of the cellular events that occur in wound healing. We investigated the direct influence of atRA on a specific target gene known to be involved in the extracellular matrix (ECM) dynamics, one of the pathways contributing to epithelial repair...
2016: Scientific Reports
C M Rosa, R Gimenes, D H S Campos, G N Guirado, C Gimenes, A A H Fernandes, A C Cicogna, R M Queiroz, I Falcão-Pires, D Miranda-Silva, P Rodrigues, F R Laurindo, D C Fernandes, C R Correa, M P Okoshi, K Okoshi
PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM)...
2016: Cardiovascular Diabetology
Carolina Añazco, Fernando Delgado-López, Paulina Araya, Ileana González, Erik Morales, Ramón Pérez-Castro, Jacqueline Romero, Armando Rojas
Gastric cancer (GC) is the fifth most frequent cancer in the world and shows the highest incidence in Latin America and Asia. An increasing amount of evidence demonstrates that lysyl oxidase isoforms, a group of extracellular matrix crosslinking enzymes, should be considered as potential biomarkers and therapeutic targets in GC. In this review, we focus on the expression levels of lysyl oxidase isoforms, its functions and the clinical implications in GC. Finding novel proteins related to the processing of these extracellular matrix enzymes might be helpful in the design of new therapies, which, in combination with classic pharmacology, could be used to delay the progress of this aggressive cancer and offer a wider temporal window for clinical intervention...
September 2016: Biomarkers in Medicine
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