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https://www.readbyqxmd.com/read/29787337/multiple-functions-of-lysyl-oxidase-like-2-in-oral-fibroproliferative-processes
#1
D Saxena, F Mahjour, A D Findlay, E A Mously, A Kantarci, P C Trackman
Gingival overgrowth is a side effect of certain medications, including calcium channel blockers, cyclosporin A, and phenytoin. Phenytoin-induced gingival overgrowth is fibrotic. Lysyl oxidases are extracellular enzymes that are required for biosynthetic cross-linking of collagens, and members of this enzyme family are upregulated in fibrosis. Previous studies in humans and in a mouse model of phenytoin-induced gingival overgrowth have shown that LOXL2 is elevated in the epithelium and connective tissue in gingival overgrowth tissues and not in normal tissues...
May 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29785119/clinical-relevance-of-lysyl-oxidase-like-2-and-functional-mechanisms-in-glioma
#2
Xiao-Guang Du, Mei-Jia Zhu
Introduction: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade ( P <0...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29759420/lysyl-oxidase-like-2-contributes-to-renal-fibrosis-in-col4%C3%AE-3-alport-mice
#3
Dominic Cosgrove, Brianna Dufek, Daniel T Meehan, Duane Delimont, Michael Hartnett, Gina Samuelson, Michael Anne Gratton, Grady Phillips, Deidre A MacKenna, Gretchen Bain
Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Here we determine whether LOXL2 influences kidney disease in COL4A3 (-/-) Alport mice. These mice were treated with a small molecule inhibitor selective for LOXL2 or with vehicle and assessed for glomerular sclerosis and fibrosis, albuminuria, blood urea nitrogen, lifespan, pro-fibrotic gene expression and ultrastructure of the glomerular basement membrane...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29755969/evaluation-of-fluorine-18-labeled-%C3%AE-1-i-n-telopeptide-analogs-as-substrate-based-radiotracers-for-pet-imaging-of-melanoma-associated-lysyl-oxidase
#4
Manuela Kuchar, Christin Neuber, Birgit Belter, Ralf Bergmann, Jens Lenk, Robert Wodtke, Torsten Kniess, Jörg Steinbach, Jens Pietzsch, Reik Löser
Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using N -succinimidyl 4-[18 F]fluorobenzoate ([18 F]SFB) as prosthetic reagent...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29746485/adiponectin-and-the-steatosis-marker-chi3l1-decrease-following-switch-to-raltegravir-compared-to-continued-pi-nnrti-based-antiretroviral-therapy
#5
Obiageli Offor, Netanya Utay, David Reynoso, Anoma Somasunderam, Judith Currier, Jordan Lake
BACKGROUND: People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor β (TGF-β) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29741670/cadmium-exposure-inhibits-branching-morphogenesis-and-causes-alterations-consistent-with-hif-1%C3%AE-inhibition-in-human-primary-breast-organoids
#6
Sabrina A Rocco, Lada Koneva, Lauren Y M Middleton, Tasha Thong, Sumeet Solanki, Sarah Karram, Kowit Nambunmee, Craig Harris, Laura S Rozek, Maureen A Sartor, Yatrik M Shah, Justin A Colacino
Developmental cadmium exposure in vivo disrupts mammary gland differentiation, while exposure of breast cell lines to cadmium causes invasion consistent with the epithelial-mesenchymal transition (EMT). The effects of cadmium on normal human breast stem cells have not been measured. Here, we quantified the effects of cadmium exposure on reduction mammoplasty patient-derived breast stem cell proliferation and differentiation. Using the mammosphere assay and organoid formation in 3D hydrogels, we tested two physiologically relevant doses of cadmium, 0...
May 7, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29732010/lysyl-oxidase-family-members-in-urological-tumorigenesis-and-fibrosis
#7
REVIEW
Tao Li, Changjing Wu, Liang Gao, Feng Qin, Qiang Wei, Jiuhong Yuan
Lysyl oxidase (LOX) is an extracellular copper-dependent monoamine oxidase that catalyzes crosslinking of soluble collagen and elastin into insoluble, mature fibers. Lysyl oxidase-like proteins (LOXL), LOX isozymes with partial structural homology, exhibit similar catalytic activities. This review summarizes recent findings describing the roles of LOX family members in urological cancers and fibrosis. LOX/LOXL play key roles in extracellular matrix stability and integrity, which is essential for normal female pelvic floor function...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29728125/matrix-stiffness-upregulated-loxl2-promotes-fibronectin-production-mmp9-and-cxcl12-expression-and-bmdcs-recruitment-to-assist-pre-metastatic-niche-formation
#8
Sifan Wu, Qiongdan Zheng, Xiaoxia Xing, Yinying Dong, Yaohui Wang, Yang You, Rongxin Chen, Chao Hu, Jie Chen, Dongmei Gao, Yan Zhao, Zhiming Wang, Tongchun Xue, Zhenggang Ren, Jiefeng Cui
BACKGROUND: Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre-metastatic niche...
May 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29709678/lysyl-oxidase-like-protein-2-loxl2-modules-barrier-function-in-cholangiocytes-in-cholestasis
#9
Marion J Pollheimer, Silvia Racedo, Amanda Mikels-Vigdal, Derek Marshall, Christopher Bowlus, Carolin Lackner, Tobias Madl, Tom H Karlsen, Johannes R Hov, Susan K Lyman, Joanne Adamkewicz, Victoria Smith, Emmanuel Moreau, Gernot Zollner, Tor Jacob Eide, Tatjana Stojakovic, Hubert Scharnagl, Hans-Jürgen Gruber, Rudolf E Stauber, Michael Trauner, Peter Fickert
BACKGROUND: The lysyl oxidase-like protein 2 (LOXL2) promotes stabilization of the extracellular matrix, chemotaxis, cell growth and cell mobility. We aimed to (i) identify stimuli of LOXL2 in cholangiopathies, (ii) characterize the effects of LOXL2 on biliary epithelial cells' (BECs) barrier function, (iii) compare LOXL2 expression in PSC, PBC, and disease controls, and (iv) to determine LOXL2 expression and cellular sources in 4 mouse models for cholangiopathies. METHODS: Cultured murine BECs were challenged with well-known triggers of cellular senescence, hypoxia, phospholipid-deficient Abcb4-/- mouse bile and chenodeoxycholic acid (CDCA) and investigated for LOXL2, SNAIL1 and E-cadherin expression and transepithelial electrical resistance (TEER) with and without LOX-inhibition...
April 27, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29627371/the-apparent-competitive-action-of-ecm-proteases-and-cross-linking-enzymes-during-fibrosis-applications-to-drug-discovery
#10
Nikolaos A Afratis, Mordehay Klepfish, Nikos K Karamanos, Irit Sagi
Progressive loss of organ function in most organs is associated with fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death. Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts...
April 5, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29620290/significance-of-lysyl-oxidase%C3%A2-like-2-gene-expression-on-the-epithelial%C3%A2-mesenchymal-status-of-hepatocellular-carcinoma
#11
Go Ninomiya, Suguru Yamada, Masamichi Hayashi, Shigeomi Takeda, Masaya Suenaga, Hideki Takami, Mitsuro Kanda, Naoki Iwata, Yukiko Niwa, Chie Tanaka, Daisuke Kobayashi, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
In the present study, we investigated the role of lysyl oxidase‑like 2 (LOXL2), the correlation between LOXL2 and epithelial to mesenchymal transition (EMT) and the effects of using β‑aminopropionitrile (BAPN) to inhibit LOXL2 with the aim of reducing tumor progression in hepatocellular carcinoma (HCC). The expression level of LOXL2 was evaluated in HCC and adjacent non‑cancerous tissues using quantitative reverse transcription polymerase chain reaction and clinicopathological analyses. The effects of BAPN on cell proliferation, migration and invasion were investigated in vitro...
April 2, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29619832/a-recombinant-human-loxl2-secreted-from-hek-cells-displays-complex-acidic-glycans-at-all-three-n-linked-glycosylation-sites
#12
Eden P Go, Hee-Jung Moon, Minae Mure, Heather Desaire
Human Lysyl oxidase-like 2 (hLOXL2), a glycoprotein implicated in tumor progression and organ fibrosis, is a molecular target for anti-cancer and anti-fibrosis treatment. This glycoprotein contains three predicted N-linked glycosylation sites; one of which is near the protein's active site and at least one more is known to facilitate the protein's secretion. Since the glycosylation impacts the protein's biology, we sought to characterize the native, mammalian glycosylation profile and to determine how closely this profile is recapitulated when the protein is expressed in insect cells...
April 5, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29434955/association-between-lysyl-oxidase-and-fibrotic-focus-in-relation-with-inflammation-in-breast-cancer
#13
Young Ju Jeong, Sung Hwan Park, Sung Hee Mun, Sang Gyu Kwak, Sun-Jae Lee, Hoon Kyu Oh
We hypothesized that lysyl oxidase (LOX) contributes to the formation of fibrotic focus (FF) in association with inflammation and serves a significant role in breast carcinogenesis. In the present study, the association between the expression of LOX family members and FF with regards to with inflammation was analyzed, and the prognostic significance of LOX and FF in breast cancer was investigated. Immunohistochemical staining for LOX, LOX-like protein (LOXL) 1, LOXL2 and LOXL3 was performed in primary breast cancer tissues...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29339785/the-lncrna-gata6-as-epigenetically-regulates-endothelial-gene-expression-via-interaction-with-loxl2
#14
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
#15
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...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29184001/pace4-proteolytically-processes-loxl2-with-little-impact-on-its-catalytic-activity
#16
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-hba-1c-levels-a-systematic-review-and-replication-in-a-case-control-sample-of-the-lifelines-study
#17
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...
February 2018: Diabetologia
https://www.readbyqxmd.com/read/29156517/mir-504-inhibits-cell-proliferation-and-invasion-by-targeting-loxl2-in-non-small-cell-lung-cancer
#18
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...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29125826/lysyl-oxidases-regulate-fibrillar-collagen-remodelling-in-idiopathic-pulmonary-fibrosis
#19
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
#20
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
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