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LOXL2

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https://www.readbyqxmd.com/read/29339785/the-lncrna-gata6-as-epigenetically-regulates-endothelial-gene-expression-via-interaction-with-loxl2
#1
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A Boon, Stefanie Dimmeler
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29207131/lysyl-oxidases-expression-and-histopathological-changes-of-the-diabetic-rat-nephron
#2
Jun Chen, Jie Ren, Wings T Y Loo, Liang Hao, Min Wang
Diabetic nephropathy (DN) is a major complication of diabetes, the accumulation of extracellular matrix (ECM) is considered an indication of nephropathological changes. Lysyl oxidases (LOXs) are also associated with ECM. However, the majority of studies on LOXs have focused on their potential role in renal fibrogenesis and there has no examination of LOXs expression or the correlation with histopathological changes of DN, including glomerular basement membrane (GBM) thickening and glomerulosclerosis. In this study, the association between histological changes and LOXs was explored using a type 2 diabetes model of male Zucker diabetic fatty rats...
November 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29184001/pace4-proteolytically-processes-loxl2-with-little-impact-on-its-catalytic-activity
#3
Kazushi Okada, Hee-Jung Moon, Joel Finney, Frédéric Couture, Robert Day, Minae Mure
Lysyl oxidase-like 2 (LOXL2) belongs to the LOX family of amine oxidases, which play a critical role in extracellular matrix remodeling by crosslinking collagen and elastin. Overexpression of LOX and/or LOXL2 drives fibrosis in several hepatic and vascular diseases, and tumor progression in some aggressive cancers. Because LOX and LOXL2 have a conserved Cterminal catalytic domain, LOXL2 is generally presumed to have the same biological activity as LOX. However, their N-termini are remarkably different and hint at potentially discrete functions and regulation...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29164275/dna-methylation-markers-associated-with-type-2-diabetes-fasting-glucose-and-hba1c-levels-a-systematic-review-and-replication-in-a-case-control-sample-of-the-lifelines-study
#4
Eliza Walaszczyk, Mirjam Luijten, Annemieke M W Spijkerman, Marc J Bonder, Helen L Lutgers, Harold Snieder, Bruce H R Wolffenbuttel, Jana V van Vliet-Ostaptchouk
AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study. METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results...
November 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/29156517/mir-504-inhibits-cell-proliferation-and-invasion-by-targeting-loxl2-in-non-small-cell-lung-cancer
#5
Ming-Fan Ye, Ji-Guang Zhang, Tian-Xing Guo, Xiao-Jie Pan
BACKGROUND: MicroRNAs (miRNAs) play crucial roles in tumor initiation and development. The aim of the study was to explore the clinicopathological role and functional effects of miR-504 in non small cell lung cancer (NSCLC). METHODS: Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was applied to detect the expression of miR-504 in 55 cases of NSCLC tissues and matched adjacent normal tissues in NSCLC patients. MTT, colony formation and transwell invasion assays were performed to evaluate the effects of miR-504 on cell proliferation and invasion, respectively...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29125826/lysyl-oxidases-regulate-fibrillar-collagen-remodelling-in-idiopathic-pulmonary-fibrosis
#6
Gavin Tjin, Eric S White, Alen Faiz, Delphine Sicard, Daniel J Tschumperlin, Annabelle Mahar, Eleanor P W Kable, Janette K Burgess
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29113306/role-of-loxl2-in-the-epithelial-mesenchymal-transition-and-colorectal-cancer-metastasis
#7
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...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107163/exome-sequencing-identifies-loxl2-mutation-as-a-cause-of-familial-intracranial-aneurysm
#8
YaQiu Wu, Zhili Li, Yi Shi, Longyi Chen, Haibin Tan, Zhenyu Wang, Cheng Yin, Ling Liu, Junting Hu
BACKGROUND: Genetic risk factors can contribute to the etiology of intracranial aneurysms (IAs) and the genetic predisposition of IAs is largely unknown. Our study is aimed to explore the role of rare variation in IA susceptibility. METHODS: Whole exome sequencing (WES) was performed in a representative family with history of multiple cases of IAs. WES variants were prioritized by various filtering strategies, including frequency, predicted pathogenicity and functional prediction...
October 26, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29089463/increased-serum-lysyl-oxidase-like-2-levels-correlate-with-the-degree-of-left-atrial-fibrosis-in-patients-with-atrial-fibrillation
#9
Yingming Zhao, Kangting Tang, Xu Tianbao, Junhong Wang, Jin Yang, Dianfu Li
Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. This study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29080554/loxl2-as-a-protective-in-osteoarthritis-cartilage
#10
Manish V Bais, Mary B Goldring
No abstract text is available yet for this article.
October 27, 2017: Aging
https://www.readbyqxmd.com/read/29052023/the-serum-level-and-significance-of-lysyl-oxidase-like-2-in-patients-with-rheumatoid-arthritis-associated-interstitial-lung-disease
#11
Qiang Fu, Yu Bai, Yuan Liu, Junfei Zhou, Yi Zheng
Our previous experiments found that lysyl oxidase-like 2 (LOXL2) may be a useful preclinical serological marker for pulmonary fibrosis in the mouse model. The role of LOXL2 in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is still unclear. We investigated whether serum LOXL2 levels are associated with RA-ILD patients. The levels of serum LOXL2 were measured by enzyme-linked immunosorbent assay in 49 RA-ILD patients (21 patients with ILD disease duration < 3 months; 28 patients with ILD disease duration > 3 months), 43 RA patients without ILD and 20 normal healthy controls...
October 19, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28965583/the-copper-dependent-lysyl-oxidases-contribute-to-the-pathogenesis-of-pulmonary-emphysema-in-chronic-obstructive-pulmonary-disease-patients
#12
Neziha Besiktepe, Ozgecan Kayalar, Ezel Ersen, Fusun Oztay
Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity...
December 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28963018/temporal-development-of-near-native-functional-properties-and-correlations-with-qmri-in-self-assembling-fibrocartilage-treated-with-exogenous-lysyl-oxidase-homolog-2
#13
Pasha Hadidi, Derek D Cissell, Jerry C Hu, Kyriacos A Athanasiou
Advances in cartilage tissue engineering have led to constructs with mechanical integrity and biochemical composition increasingly resembling that of native tissues. In particular, collagen cross-linking with lysyl oxidase has been used to significantly enhance the mechanical properties of engineered neotissues. In this study, development of collagen cross-links over time, and correlations with tensile properties, were examined in self-assembling neotissues. Additionally, quantitative MRI metrics were examined in relation to construct mechanical properties as well as pyridinoline cross-link content and other engineered tissue components...
December 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28872461/fibroblast-specific-inhibition-of-tgf-%C3%AE-1-signaling-attenuates-lung-and-tumor-fibrosis
#14
Ying Wei, Thomas J Kim, David H Peng, Dana Duan, Don L Gibbons, Mitsuo Yamauchi, Julia R Jackson, Claude J Le Saux, Cheresa Calhoun, Jay Peters, Rik Derynck, Bradley J Backes, Harold A Chapman
TGF-β1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-β1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-β1-induced epithelial-mesenchymal transition without immediate TGF-β1 receptor (TβR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28864775/proteolytic-processing-of-lysyl-oxidase-like-2-in-the-extracellular-matrix-is-required-for-crosslinking-of-basement-membrane-collagen-iv
#15
Alberto J López-Jiménez, Trayambak Basak, Roberto M Vanacore
Lysyl oxidase-like-2 (LOXL2) is an enzyme secreted into the extracellular matrix that crosslinks collagens by mediating oxidative deamination of lysine residues. Our previous work demonstrated that this enzyme crosslinks the 7S domain, a structural domain that stabilizes collagen IV scaffolds in the basement membrane. Despite its relevant role in extracellular matrix biosynthesis, little is known about the structural requirements of LOXL2 that enable collagen IV crosslinking. In this study, we demonstrate that LOXL2 is processed extracellularly by serine proteases, generating a 65-kDa form lacking the first two scavenger receptor cysteine-rich domains...
October 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28859141/asporin-deficient-mice-have-tougher-skin-and-altered-skin-glycosaminoglycan-content-and-structure
#16
Marco Maccarana, René B Svensson, Anki Knutsson, Antonis Giannopoulos, Mea Pelkonen, MaryAnn Weis, David Eyre, Matthew Warman, Sebastian Kalamajski
The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28829846/racial-differences-in-the-extracellular-matrix-and-histone-acetylation-of-the-lamina-cribrosa-and-peripapillary-sclera
#17
Hae-Young Lopilly Park, Jie Hyun Kim, Younhea Jung, Chan Kee Park
Purpose: We investigated the extracellular matrix (ECM) of the lamina cribrosa (LC) and peripapillary sclera (PPS) and compared histone acetylation and related enzymes to identify racial differences between Korean and Caucasian donor eyes. Methods: Posterior segment tissues were obtained from 30 Caucasian donors and 42 age and axial length-matched Korean donors. Histone modification was assessed for histone deacetylase (HDAC) 2, HDAC3, and acetylated histone H3...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28782046/circulating-loxl2-levels-reflect-severity-of-intestinal-fibrosis-and-galt-cd4-t-lymphocyte-depletion-in-treated-hiv-infection
#18
Sophie Seang, Anoma Somasunderam, Maitreyee Nigalye, Ma Somsouk, Timoty W Schacker, Joyce L Sanchez, Peter W Hunt, Netanya S Utay, Jordan E Lake
BACKGROUND: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4(+) T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. METHODS: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28764769/anabolic-role-of-lysyl-oxidase-like-2-in-cartilage-of-knee-and-temporomandibular-joints-with-osteoarthritis
#19
Weam Alshenibr, Mustafa M Tashkandi, Saqer F Alsaqer, Yazeed Alkheriji, Amelia Wise, Sadanand Fulzele, Pushkar Mehra, Mary B Goldring, Louis C Gerstenfeld, Manish V Bais
BACKGROUND: Lysyl oxidase like-2 (LOXL2) is a copper-dependent amine oxidase. Our previous studies showed that LOXL2 is elevated during mouse fracture healing. The goal of this study was to evaluate the potential of LOXL2 to act as an anabolic agent in cartilage affected by osteoarthritis (OA). METHODS: LOXL2 was visualized in tissues from human knee and hip joints and temporomandibular joints (TMJ) by immunofluorescence. The activity of LOXL2 in human articular and TMJ chondrocytes was assessed by cell-based assays, microarray analysis, and RT-qPCR, and LOXL2-mediated activation of NF-κB and extracellular signal-related kinase (ERK) signaling pathways was measured by western blotting...
August 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28720577/lysyl-oxidase-like-protein-loxl2-promotes-lung-metastasis-of-breast-cancer
#20
Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vázquez-Naharro, Patricia G Santamaria, Saleta Morales, Pierre R 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...
November 1, 2017: Cancer Research
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