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Lysyl oxidase like 1

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
Kazuto Kamikawaji, Naohiko Seki, Masaki Watanabe, Hiroko Mataki, Tomohiro Kumamoto, Koichiro Takagi, Keiko Mizuno, Hiromasa Inoue
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells...
August 4, 2016: Journal of Human Genetics
Léa Moulin, Valérie Cenizo, Alengo Nyamay Antu, Valérie Andre-Frei, Sabine Pain, Pascal Sommer, Romain Debret
Lysyl oxidase-like 1 (LOXL1) is an amino-oxidase involved in maturation of elastic fibres. Its downregulation has been associated with elastic fibres repair loss in ageing aorta, lung, ligament and skin. Several evidences of LOXL1 epigenetic silencing by promoter methylation were reported in cancer and cutis laxa syndrome. We hypothesised that this mechanism could be implicated in skin ageing process, as far as elastic fibres are also concerned. Anti-DNMT3A chromatin immuno-precipitation was conducted with nuclear extracts from skin fibroblasts isolated from young and elderly individuals, and showed a higher level of DNMT3A protein binding to the LOXL1 promoter in older cells concomitantly to the decrease of LOXL1 mRNA expression and the increase of LOXL1 promoter methylation...
July 10, 2016: Rejuvenation Research
Damien Bergeat, Alain Fautrel, Bruno Turlin, Aude Merdrignac, Michel Rayar, Karim Boudjema, Cédric Coulouarn, Laurent Sulpice
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC...
June 15, 2016: Journal of Surgical Research
Joon Seong Park, Ji-Hae Lee, Yun Sun Lee, Jae Keun Kim, Seung Myung Dong, Dong Sup Yoon
Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in cancer. We analyzed the prognostic impact of LOXL2 in pancreatic cancer patients and investigated the role of LOXL2 in pancreatic cancer cell lines. Immunohistochemical analysis was performed in samples from 80 patients and showed LOXL2 expression in 81.2% of patients with pancreatic cancer. Regarding recurrence patterns, LOXL2-positive tumors showed a significantly higher rate of distant recurrence. The 1-year and 3-year disease-free survival rates were 84...
July 5, 2016: Oncotarget
John T Benjamin, Riet van der Meer, Amanda M Im, Erin J Plosa, Rinat Zaynagetdinov, Ankita Burman, Madeline E Havrilla, Linda A Gleaves, Vasiliy V Polosukhin, Gail H Deutsch, Hiromi Yanagisawa, Jeffrey M Davidson, Lawrence S Prince, Lisa R Young, Timothy S Blackwell
The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality...
July 2016: American Journal of Pathology
Shiwani Sharma, Sarah Martin, Matthew J Sykes, Alpana Dave, Alex W Hewitt, Kathryn P Burdon, Maurizio Ronci, Nicolas H Voelcker, Jamie E Craig
Pseudoexfoliation (PEX) syndrome is a systemic disease involving the extracellular matrix. It increases the risk of glaucoma, an irreversible cause of blindness, and susceptibility to heart disease, stroke and hearing loss. Single nucleotide polymorphisms (SNPs) in the LOXL1 (Lysyl oxidase-like 1) gene are the major known genetic risk factor for PEX syndrome. Two coding SNPs, rs1048861 (G > T; Arg141Leu) and rs3825942 (G > A; Gly153Asp), in the LOXL1 gene are strongly associated with the disease risk in multiple populations worldwide...
May 2016: Experimental Eye Research
Alexios A Panoutsopoulos, Vassiliki S Gartaganis, Marios P Giannakopoulos, Panos D Goumas, Evangelos D Anastassiou, Sotirios P Gartaganis
PURPOSE: The aim of this study was to determine the possible association of rs1048661 and rs3825942 single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene of cataract patients from southwestern Greece with pseudoexfoliation (PEX) syndrome. PATIENTS AND METHODS: Ninety-three patients with PEX syndrome and 74 without PEX syndrome were recruited with the principal diagnosis being cataract. LOXL1 SNPs, rs1048661 and rs3825942, were genotyped by using polymerase chain reaction...
2016: Clinical Ophthalmology
Nathan Kow, Beri Ridgeway, Mei Kuang, Robert S Butler, Margot S Damaser
OBJECTIVES: This study aimed to compare cellular expression of lysyl oxidase-like 1 (LOXL1), a key enzyme in elastin metabolism, of premenopausal women with pelvic organ prolapse (POP) compared with premenopausal controls without POP and postmenopausal women with POP. In addition, we examined whether variation of LOXL1 expression was dependent on biopsy site. METHODS: A standardized protocol was utilized to obtain vaginal biopsies from 30 women (10 premenopausal POP, 10 postmenopausal POP, and 10 premenopausal non-POP)...
July 2016: Female Pelvic Medicine & Reconstructive Surgery
Maria Nilsson, Hanibal Adamo, Anders Bergh, Sofia Halin Bergström
Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth...
2016: Scientific Reports
Suzan Guven Yilmaz, Melis Palamar, Huseyin Onay, Orhan Ilim, Ayca Aykut, Feristah Ferda Ozkinay, Ayse Yagci
The purpose of this study is to evaluate whole lysyl oxidase like 1 (LOXL1) gene by sequence analysis in Turkish patients with exfoliation glaucoma (XFG). A total of 48 (35 male, 13 female) patients with XFG were enrolled. Besides routine ophthalmological examination, peripapillary retinal nerve fibre layer (RNFL) analysis with optic coherence tomography was performed. Blood samples of 2 ml with EDTA were obtained and sent to Medical Genetics Department, Molecular Genetics Laboratory for LOXL1 polymorphism (PCR and agarose gel imaging) analysis...
October 2016: International Ophthalmology
Louis R Pasquale, Terete Borrás, John H Fingert, Janey L Wiggs, Robert Ritch
PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion...
September 2016: Acta Ophthalmologica
Loai Alsofi, Eileen Daley, Ian Hornstra, Elise F Morgan, Zachary D Mason, Jesus F Acevedo, R Ann Word, Louis C Gerstenfeld, Philip C Trackman
Lysyl oxidases are required for collagen and elastin cross-linking and extracellular matrix maturation including in bone. The lysyl oxidase family consists of lysyl oxidase (LOX) and 4 isoforms (LOXL1-4). Here we investigate whether deletion of LOXL1, which has been linked primarily to elastin maturation, leads to skeletal abnormalities. Left femurs (n = 8), L5 vertebrae (n = 8), and tibiae (n = 8) were analyzed by micro-computed tomography in 13-week-old wild-type (WT) and LOXL1-/- male and female mice. Right femurs (n = 8) were subjected to immunohistochemistry for LOXL1, and histochemical/histology analyses of osteoclasts and growth plates...
February 2016: Calcified Tissue International
Wen Zong, Yan Jiang, Jing Zhao, Jian Zhang, Jian-gang Gao
The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells...
October 2015: Journal of Zhejiang University. Science. B
Haibin Li, Mingxing Lei, Can Yu, Yonggang Lv, Yang Song, Li Yang
PURPOSES: This study investigated whether mechano growth factor-E (MGF-E) peptide can regulate apoptosis and inflammation responses in fibroblast-like synoviocytes of osteoarthritis (OA). METHODS: A (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay was performed to evaluate cytotoxic effects of exogenous MGF-E peptide on OA fibroblast-like synoviocytes (OA-FLS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to check messenger RNA (mRNA) expression levels of lysyl oxidase (LOX) family members (LOX) after OA-FLS treatment using MGF-E peptide...
December 2015: International Orthopaedics
Lydia Álvarez, Montserrat García, Héctor González-Iglesias, Julio Escribano, Pedro P Rodríguez-Calvo, Luis Fernández-Vega, Miguel Coca-Prados
BACKGROUND: LOXL1 gene is the most important genetic risk factor known so far for pseudoexfoliation glaucoma (XFG). Our purpose was to evaluate the potential association of individual genetic variants of the lysyl oxidase-like 1 (LOXL1) gene and haplotypes with XFG in Spanish patients. METHODS: Blood samples were collected from a total of 105 Spanish patients with XFG and 200 healthy controls. The entire LOXL1 gene along with the promoter, coding and non-coding regions including the 5'- and 3'-untranslated regions, were sequenced using next-generation sequencing in 99 XFG patients...
2015: BMC Medical Genetics
Michael A Hauser, Inas F Aboobakar, Yutao Liu, Shiroh Miura, Benjamin T Whigham, Pratap Challa, Joshua Wheeler, Andrew Williams, Cecelia Santiago-Turla, Xuejun Qin, Robyn M Rautenbach, Ari Ziskind, Michèle Ramsay, Steffen Uebe, Lingyun Song, Alexias Safi, Eranga N Vithana, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Ken Hayashi, Shin-ichi Manabe, Shigeyasu Kazama, Yosai Mori, Kazunori Miyata, Nagahisa Yoshimura, Andre Reis, Gregory E Crawford, Francesca Pasutto, Trevor R Carmichael, Susan E I Williams, Mineo Ozaki, Tin Aung, Chiea-Chuen Khor, W Daniel Stamer, Allison E Ashley-Koch, R Rand Allingham
Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls...
November 15, 2015: Human Molecular Genetics
Melinda Wuest, Manuela Kuchar, Sai Kiran Sharma, Susan Richter, Ingrit Hamann, Monica Wang, Larissa Vos, John R Mackey, Frank Wuest, Reik Löser
INTRODUCTION: Lysyl oxidase (LOX; ExPASy ENZYME entry: EC and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer...
August 13, 2015: Breast Cancer Research: BCR
Tine Van Bergen, Rhyannon Spangler, Derek Marshall, Karolien Hollanders, Sara Van de Veire, Evelien Vandewalle, Lieve Moons, Jean Herman, Victoria Smith, Ingeborg Stalmans
PURPOSE: We investigated whether lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2) play a role in an experimental model of choroidal neovascularization (CNV). The therapeutic potential of antibodies against LOX (M64) and LOXL2 (AB0023) was evaluated in a murine laser-induced CNV model. METHODS: Expression of LOX and LOXL2 in the posterior eye cups (including retina, retinal pigment epithelium, choroid, and sclera) was studied by qRT-PCR and immunohistochemistry...
August 2015: Investigative Ophthalmology & Visual Science
Wan-Chun Chen, Hsi-Hui Lin, Ming-Jer Tang
The proliferation of mouse proximal tubular epithelial cells in ex vivo culture depends on matrix stiffness. Combined analysis of the microarray and experimental data revealed that Krüppel-like factor (Klf)5 was the most up-regulated transcription factor accompanied by the down-regulation of Klf4 when cells were on stiff matrix. These changes were reversed by soft matrix via extracellular signal-regulated kinase (ERK) inactivation. Knockdown of Klf5 or forced expression of Klf4 inhibited stiff matrix-induced cell spreading and proliferation, suggesting that Klf5/Klf4 act as positive and negative regulators, respectively...
September 2015: American Journal of Pathology
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