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lysyl oxidase

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https://www.readbyqxmd.com/read/28720577/lysyl-oxidase-like-protein-loxl2-promotes-lung-metastasis-of-breast-cancer
#1
Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vazquez-Naharro, Patricia G Santamaría, Saleta Morales, Pierre Dubus, Laura Muinelo-Romay, Rafael López López, Jason C Tung, Valerie M Weaver, Francisco Portillo, Amparo Cano
The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28715234/is-cardiovascular-disease-in-patients-with-diabetes-associated-with-serum-levels-of-mmp-2-lox-and-the-elastin-degradation-products-elm-and-elm-2
#2
Simone Andrea Rørdam Preil, Anne-Sofie Faarvang Thorsen, Anne Lindegaard Christiansen, Mikael Kjær Poulsen, Morten Asser Karsdal, Diana Julie Leeming, Lars Melholt Rasmussen
BACKGROUND: Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in diabetic patients, namely matrix metalloproteinase 2 (MMP-2), lysyl oxidase (LOX) and elastin itself. In this study we investigate whether the serum concentrations of elastin-related proteins correlate to signs of CVD in patients with T2DM...
July 17, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28711328/overexpression-of-microrna-30a-contributes-to-the-development-of-aortic-dissection-by-targeting-lysyl-oxidase
#3
Yang Yu, Enyi Shi, Tianxiang Gu, Rui Tang, Shilun Gao, Yongchao Wang, Hongbo Liu
OBJECTIVE: To explore the role of microRNA (miR)-30a in the development of aortic dissection. METHODS: Human aortic specimens of aortic dissections and aneurysms were harvested. Aortic specimens from donors for heart transplantation served as controls. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with agomiR-30a or antagomiR-30a, and control cells were incubated with empty vectors. Rats were pretreated with agomiR-30a or antagomiR-30a (5 × 10(7) transfection units every 3 days for 4 weeks), and empty vectors were infused to controls...
June 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28698228/perturbations-to-lysyl-oxidase-expression-broadly-influence-the-transcriptome-of-lung-fibroblasts
#4
Ivana Mižíková, Francesco Palumbo, Tamás Tábi, Susanne Herold, István Vadász, Konstantin Mayer, Werner Seeger, Rory E Morty
Lysyl oxidases are credited with pathogenic roles in lung diseases, including cancer, fibrosis, pulmonary hypertension, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). Lysyl oxidases facilitate the covalent intra- and inter-molecular cross-linking of collagen and elastin fibers, thereby imparting tensile strength to the extracellular matrix (ECM). Alternative ECM-independent roles have recently been proposed for lysyl oxidases, including regulation of growth factor signaling, chromatin remodeling, and transcriptional regulation; all of which impact cell phenotype...
July 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28693740/new-mechanisms-of-vascular-fibrosis-role-of-lysyl-oxidase
#5
José A Páramo
No abstract text is available yet for this article.
July 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28689812/ibmx-protects-human-proximal-tubular-epithelial-cells-from-hypoxic-stress-through-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#6
Arif Ul Hasan, Wararat Kittikulsuth, Fuminori Yamaguchi, Tuba Musarrat Ansary, Asadur Rahman, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Masaaki Tokuda, Akira Nishiyama
Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also increased the cellular cyclic adenosine monophosphate (cAMP) level...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28689747/hypoxia-inhibits-growth-proliferation-and-increases-response-to-chemotherapy-in-retinoblastoma-cells
#7
Qian Yang, Arushi Tripathy, Wayne Yu, Charles G Eberhart, Laura Asnaghi
Retinoblastoma is a malignant tumor of the retina and the most frequent intraocular cancer in children. Low oxygen tension (hypoxia) is a common phenomenon in advanced retinoblastomas, but its biological effect on retinoblastoma growth is not clearly understood. Here we studied how hypoxia altered retinoblastoma gene expression and modulated growth and response to chemotherapy. The hypoxic marker lysyl oxidase (LOX) was expressed in 8 of 12 human retinoblastomas analyzed by immunohistochemistry, suggesting that a hypoxic microenvironment is present in up to two thirds of the cases...
July 6, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28683690/using-costal-chondrocytes-to-engineer-articular-cartilage-with-applications-of-passive-axial-compression-and-bioactive-stimuli
#8
Le Huwe, Gurdeep Sullan, Jerry C Hu, Kyriacos A Athanasiou
Generating neocartilage with suitable mechanical integrity from a cell source that can circumvent chondrocyte scarcity is indispensable for articular cartilage regeneration strategies. Costal chondrocytes of the rib eliminate donor site morbidity in the articular joint, but it remains unclear how neocartilage formed from these cells responds to mechanical loading, especially if the intent is to use it in a load-bearing joint. In a series of three experiments, this study sought to determine efficacious parameters of passive axial compressive stimulation that would enable costal chondrocytes to synthesize mechanically robust cartilage...
July 6, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28677767/lysyl-oxidase%C3%A2-like-2-is-expressed-in-kidney-tissue-and-is-associated-with-the-progression-of-tubulointerstitial-fibrosis
#9
Sung-Eun Choi, Nara Jeon, Hoon Young Choi, Jae Il Shin, Hyeon Joo Jeong, Beom Jin Lim
Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis...
July 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28668305/detrimental-role-of-lysyl-oxidase-in-cardiac-remodeling
#10
Elia C El Hajj, Milad C El Hajj, Van K Ninh, Jessica M Bradley, Mario A Claudino, Jason D Gardner
A key feature of heart failure is adverse extracellular matrix (ECM) remodeling, which is associated with increases in the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we assess the progression of cardiovascular remodeling from the compensatory to decompensatory phase, with a focus on the change in LOX expression and activity as it relates to alterations in ECM composition and changes in cardiac function. Adult male Sprague-Dawley rats were studied after 4, 14, or 21weeks of aortocaval fistula-induced volume overload (VO)...
June 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28660757/pulsed-epr-insights-into-the-ligand-environment-of-copper-in-drosophila-lysyl-oxidase
#11
Guodong Rao, Sandhya Bansal, Wen Xuan Law, Bing O'Dowd, Sergei A Dikanov, Eric Oldfield
Lysyl oxidase is a copper amine oxidase that crosslinks collagens and elastin in connective tissue and plays an important role in fibrosis, cancer development and formation of the "metastatic niche". Despite its important biological functions, the structure of human LOX remains unknown (unlike that of an unrelated LOX, from Pichia pastoris). Here, we expressed active LOX from Drosophila melanogaster, DmLOXL1, a close homologue of human LOX, and characterized it by MS, UV-Vis, activity and inhibition assays...
June 29, 2017: Biochemistry
https://www.readbyqxmd.com/read/28638462/reorganized-collagen-in-the-tumor-microenvironment-of-gastric-cancer-and-its-association-with-prognosis
#12
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
#13
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). Here, 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...
August 19, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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