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Lysyl oxidase-like 2

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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
#1
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
#2
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/29615815/cardiac-myo-fibroblasts-modulate-the-migration-of-monocyte-subsets
#3
Kathleen Pappritz, Konstantinos Savvatis, Annika Koschel, Kapka Miteva, Carsten Tschöpe, Sophie Van Linthout
Cardiac fibroblasts play an important role in the regulation of the extracellular matrix and are newly recognized as inflammatory supporter cells. Interferon (IFN)-γ is known to counteract transforming growth factor (TGF)-ß1-induced myofibroblast differentiation. This study aims at investigating in vitro how IFN-γ affects TGF-ß1-induced monocyte attraction. Therefore, C4 fibroblasts and fibroblasts obtained by outgrowth culture from the left ventricle (LV) of male C57BL6/j mice were stimulated with TGF-β1, IFN-γ and TGF-β1 + IFN-γ...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29581294/crystal-structure-of-human-lysyl-oxidase-like-2-hloxl2-in-a-precursor-state
#4
Xi Zhang, Qifan Wang, Jianping Wu, Jiawei Wang, Yigong Shi, Minhao Liu
Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29547702/inhibition-of-enzymes-involved-in-collagen-cross-linking-reduces-vascular-smooth-muscle-cell-calcification
#5
Eva Jover, Ana Silvente, Francisco Marín, José Martínez-González, Mar Orriols, Carlos M Martinez, Carmen María Puche, Mariano Valdés, Cristina Rodriguez, Diana Hernández-Romero
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia (HPM)-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by HPM conditioning...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29532123/collagen-xviii-and-loxl-4-polymorphisms-in-women-with-and-without-advanced-pelvic-organ-prolapse
#6
Renata G M Dos Santos, Fernanda C A Pepicelli, Nilce C Batista, Cristina V de Carvalho, Maria A T Bortolini, Rodrigo A Castro
INTRODUCTION AND HYPOTHESIS: We verified the presence of single nucleotide polymorphisms (SNP) rs2236479 of the collagen 18 (COL18A1) and rs2862296 of the lysyl oxidase-like 4 (LOXL-4) genes and the association with pelvic organ prolapse (POP) in Brazilian women and determined risk factors for POP development. METHODS: We assessed 532 postmenopausal women divided into POP (stages III and IV) and control (stages 0 and I) groups by examination and peripheral blood sample collection...
March 12, 2018: International Urogynecology Journal
https://www.readbyqxmd.com/read/29513553/anterior-cruciate-ligament-transection-induced-cellular-and-extracellular-events-in-menisci-implications-for-osteoarthritis
#7
Jing Xie, Demao Zhang, Yunfeng Lin, Quan Yuan, Xuedong Zhou
BACKGROUND: The meniscus plays an important role in knee joint diseases such as osteoarthritis (OA). Meniscal injuries can be accompanied by joint catabolic events initiated by inflammation, leading to articular cartilage destruction, but the cellular events responsible for intrinsic meniscal injury and the extracellular matrix changes necessary for meniscal degradation are not well known. PURPOSE: To explore the cellular and matrix-related changes of menisci based on a mouse OA model of anterior cruciate ligament transection (ACLT)...
March 1, 2018: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29450398/cataract-surgery-outcome-in-patients-with-non-glaucomatous-pseudoexfoliation
#8
Praveen Venkatesha Sastry, Anuj Kumar Singal
Aim. To study the outcome of cataract surgery in eyes with pseudoexfoliation without signs of glaucoma. Methods. This prospective study was done over nine months on patients with pseudoexfoliation undergoing small incision cataract surgery. Only patients with normal intraocular pressure (Central Corneal Thickness Corrected), normal cup disc ratio and open angles were included. Patients on anti-glaucoma medication were excluded. Patients underwent surgery performed by a single senior surgeon. Intraoperative and postoperative day (POD) 1 findings were noted...
July 2017: Romanian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29432335/extracellular-matrix-regulation-and-dysregulation-in-exfoliation-syndrome
#9
Matthias Zenkel
Several lines of evidence, such as ultrastructural signs for activated fibrillogenesis and excessive production of elastic microfibrillar components in the anterior segment of the eye and throughout the body, indicate that exfoliation syndrome (XFS) is an elastic microfibrillopathy, leading to the accumulation of an abnormal extracellular fibrillar material (XFM). The upregulation of elastic microfibrillar components is paralleled by the selective upregulation of the cross-linking enzyme lysyl oxidase-like 1 (LOXL1) in the early phase of the disease, suggesting that LOXL1 participates in the stabilization of newly synthesized elastic proteins and finally in the stable accumulation of XFM...
February 9, 2018: Journal of Glaucoma
https://www.readbyqxmd.com/read/29432334/mechanisms-of-glaucoma-in-exfoliation-syndrome
#10
Mineo Ozaki
The most important characteristic of exfoliation syndrome (XFS) is that it involves a greater risk of developing glaucoma. In comparison with other forms of open-angle glaucoma, exfoliation glaucoma (XFG) is more resistant to medical therapy and progresses faster. Possible pathological mechanisms of glaucoma development in XFS comprise: (1) elevated intraocular pressure (IOP) caused by functional impairment of aqueous humor outflow due to deposition of exfoliation material (XFM) in the trabecular meshwork and trabecular cell dysfunction, (2) XFS-associated connective tissue elastosis leading to structural and functional alterations of the lamina cribrosa which increases the vulnerability toward elevated IOP and development of glaucomatous optic neuropathy, (3) elevated IOP due to closure of the anterior chamber angle accompanied by forward displacement of the crystalline lens due to zonular weakness, (4) presumable primary functional impairment of retinal ganglion cells...
February 9, 2018: Journal of Glaucoma
https://www.readbyqxmd.com/read/29366776/inhibition-of-lysyl-oxidase-like-1-loxl1-expression-arrests-liver-fibrosis-progression-in-cirrhosis-by-reducing-elastin-crosslinking
#11
Wenshan Zhao, Aiting Yang, Wei Chen, Ping Wang, Tianhui Liu, Min Cong, Anjian Xu, Xuzhen Yan, Jidong Jia, Hong You
Mature crosslinked-poly-elastin deposition has been found to be associated with liver fibrosis. However, the regulation of crosslinked/insoluble elastin in liver fibrosis remains largely unknown. Here, we investigated the contribution of lysyl oxidases (LOXs) family, mediated elastin crosslinking, to liver fibrogenesis. We established carbon tetrachloride (CCl4)-induced liver fibrotic and cirrhotic models and found that crosslinked/insoluble elastin levels spiked only in cirrhosis stage during disease progression, in comparison to collagen Ι levels which increased continuously though all stages...
January 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29352658/role-of-hypoxia-inducible-factor-1-in-the-development-of-renal-fibrosis-in-mouse-obstructed-kidney-special-references-to-hif-1-dependent-gene-expression-of-profibrogenic-molecules
#12
Kazuya Kabei, Yu Tateishi, Masakazu Nozaki, Masako Tanaka, Masayuki Shiota, Mayuko Osada-Oka, Shunji Nishide, Junji Uchida, Tatsuya Nakatani, Shuhei Tomita, Katsuyuki Miura
The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO...
January 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29207131/lysyl-oxidases-expression-and-histopathological-changes-of-the-diabetic-rat-nephron
#13
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
#14
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/29164236/posttranscriptional-regulation-of-loxl1-expression-via-alternative-splicing-and-nonsense-mediated-mrna-decay-as-an-adaptive-stress-response
#15
Daniel Berner, Matthias Zenkel, Francesca Pasutto, Ursula Hoja, Panah Liravi, Gabriele C Gusek-Schneider, Friedrich E Kruse, Johannes Schödel, Andre Reis, Ursula Schlötzer-Schrehardt
Purpose: Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors. Methods: Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29113306/role-of-loxl2-in-the-epithelial-mesenchymal-transition-and-colorectal-cancer-metastasis
#16
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/29089463/increased-serum-lysyl-oxidase-like-2-levels-correlate-with-the-degree-of-left-atrial-fibrosis-in-patients-with-atrial-fibrillation
#17
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. The present 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...
December 22, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29053339/ecm-crosslinking-enhances-fibroblast-growth-and-protects-against-matrix-proteolysis-in-lung-fibrosis
#18
Christopher J Philp, Ivonne Siebeke, Debbie Clements, Suzanne Miller, Anthony Habgood, Alison E John, Vidya Navaratnam, Richard B Hubbard, Gisli Jenkins, Simon R Johnson
Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is abnormally cross-linked which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover...
October 20, 2017: American Journal of Respiratory Cell and Molecular Biology
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
#19
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...
January 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#20
Andrew Camardo, Dhruv Seshadri, Tom Broekelmann, Robert Mecham, Anand Ramamurthi
Growth of abdominal aortic aneurysms (AAA), localized aortal wall expansions, is driven by the disruption and subsequent loss of aortal wall elastic fibers by matrix metalloproteases (MMPs). Since elastic fibers do not naturally regenerate or repair, arresting/reversing AAA growth has not been possible. Previously, we showed utility of doxycycline (DOX), an MMP inhibitor drug, to stimulate elastic matrix neoassembly and crosslinking at low microgram per milliliter doses in addition to inhibiting MMPs. We currently show in aneurysmal smooth muscle cell (SMC) cultures that effects of exogenous DOX in this dose range are linked to its upregulation of transforming growth factor beta (TGF-β1) via its inhibition of the regulatory protein c-Jun-N-terminal kinase 2 (JNK 2)...
September 5, 2017: Drug Delivery and Translational Research
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