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Lysyl oxidase-like 2

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https://www.readbyqxmd.com/read/29207131/lysyl-oxidases-expression-and-histopathological-changes-of-the-diabetic-rat-nephron
#1
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
#2
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
#3
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
#4
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
#5
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/29053339/ecm-crosslinking-enhances-fibroblast-growth-and-protects-against-matrix-proteolysis-in-lung-fibrosis
#6
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
#7
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/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#8
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
https://www.readbyqxmd.com/read/28872461/fibroblast-specific-inhibition-of-tgf-%C3%AE-1-signaling-attenuates-lung-and-tumor-fibrosis
#9
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
#10
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/28829846/racial-differences-in-the-extracellular-matrix-and-histone-acetylation-of-the-lamina-cribrosa-and-peripapillary-sclera
#11
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/28764769/anabolic-role-of-lysyl-oxidase-like-2-in-cartilage-of-knee-and-temporomandibular-joints-with-osteoarthritis
#12
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/28683690/using-costal-chondrocytes-to-engineer-articular-cartilage-with-applications-of-passive-axial-compression-and-bioactive-stimuli
#13
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
#14
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...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28638462/reorganized-collagen-in-the-tumor-microenvironment-of-gastric-cancer-and-its-association-with-prognosis
#15
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/28598820/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...
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
#17
Francis M 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 five groups: 1) control, 2) sham, 3) BOO + vehicle, 4) BOO + the NLRP3 inhibitor glyburide, or 5) BOO + the IL-1β receptor antagonist anakinra...
September 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#18
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28471663/identification-of-4-aminomethyl-6-trifluoromethyl-2-phenoxy-pyridine-derivatives-as-potent-selective-and-orally-efficacious-inhibitors-of-the-copper-dependent-amine-oxidase-lysyl-oxidase-like-2-loxl2
#19
Martin W Rowbottom, Gretchen Bain, Imelda Calderon, Taylor Lasof, David Lonergan, Andiliy Lai, Fei Huang, Janice Darlington, Patricia Prodanovich, Angelina M Santini, Christopher D King, Lance Goulet, Kristen E Shannon, Gina L Ma, Katherine Nguyen, Deidre A MacKenna, Jilly F Evans, John H Hutchinson
LOXL2 catalyzes the oxidative deamination of ε-amines of lysine and hydroxylysine residues within collagen and elastin, generating reactive aldehydes (allysine). Condensation with other allysines or lysines drives the formation of inter- and intramolecular cross-linkages, a process critical for the remodeling of the ECM. Dysregulation of this process can lead to fibrosis, and LOXL2 is known to be upregulated in fibrotic tissue. Small-molecules that directly inhibit LOXL2 catalytic activity represent a useful option for the treatment of fibrosis...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28468951/insulin-resistance-promotes-lysyl-oxidase-like-2-induction-and-fibrosis-accumulation-in-non-alcoholic-fatty-liver-disease
#20
Paola Dongiovanni, Marica Meroni, Guido Alessandro Baselli, Giulia Alessandra Bassani, Raffaela Rametta, Alessandro Pietrelli, Marco Maggioni, Federica Facciotti, Valentina Trunzo, Sara Badiali, Silvia Fargion, Stefano Gatti, Luca Valenti
In patients with non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) associates with fibrosis progression independently of the hepatic inflammation, but the mechanisms are still unclear. We modeled the independent contribution of inflammation (non-alcoholic steatohepatitis: NASH) by exploiting the methionine-choline deficient (MCD) diet, and that of IR by insulin receptor (InsR) haploinsufficiency (InsR+/-) in the pathogenesis of liver fibrosis in C57BL/6 mice. We confirmed the study findings in 96 patients with NAFLD...
June 1, 2017: Clinical Science (1979-)
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