keyword
MENU ▼
Read by QxMD icon Read
search

Lysyl oxidase-like 2

keyword
https://www.readbyqxmd.com/read/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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-)
https://www.readbyqxmd.com/read/28452589/lysyl-oxidase-propeptide-promotes-adipogenesis-through-inhibition-of-fgf-2-signaling
#14
John D Griner, Carl J Rogers, Mei-Jun Zhu, Min Du
Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine residues in collagen and elastin, key components of connective tissue. LOX is synthesized as an inactive 50 kD pre-proenzyme, and secreted to the extracellular matrix where it is cleaved into an active 32 kD LOX, and an 18kD free propeptide (LOX-PP), purportedly an inhibitor of fibroblast growth factor-2 (FGF-2) signaling. Given that adipocytes are distributed inside the connective tissue, it is likely that LOX-PP has an important regulatory role in adipogenesis, which has not been studied...
January 2, 2017: Adipocyte
https://www.readbyqxmd.com/read/28449718/hif-1%C3%AE-promoted-vasculogenic-mimicry-formation-in-hepatocellular-carcinoma-through-loxl2-up-regulation-in-hypoxic-tumor-microenvironment
#15
Meili Wang, Xiulan Zhao, Dongwang Zhu, Tieju Liu, Xiaohui Liang, Fang Liu, Yanhui Zhang, Xueyi Dong, Baocun Sun
BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) have steadily increased in recent years. A hypoxic microenvironment is one of the most important characteristics of solid tumors which has been shown to promote tumor metastasis, epithelial-mesenchymal transition and angiogenesis. Epithelial-mesenchymal transition and vasculogenic mimicry have been regarded as crucial contributing factors to cancer progression. HIF-1α functions as a master transcriptional regulator in the adaptive response to hypoxia...
April 27, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28435530/small-molecule-lysyl-oxidase-like-2-loxl2-inhibitors-the-identification-of-an-inhibitor-selective-for-loxl2-over-lox
#16
John H Hutchinson, Martin W Rowbottom, David Lonergan, Janice Darlington, Pat Prodanovich, Christopher D King, Jilly F Evans, Gretchen Bain
Two series of novel LOXL2 enzyme inhibitors are described: benzylamines substituted with electron withdrawing groups at the para-position and 2-substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin-4-yl)methanamine 20 (hLOXL2 IC50 = 126 nM), was shown to be selective for LOXL2 over LOX and three other amine oxidases (MAO-A, MAO-B, and SSAO). Compound 20 is the first published small molecule inhibitor selective for LOXL2 over LOX.
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28350101/loxl3-sv2-a-novel-variant-of-human-lysyl-oxidase-like-3-loxl3-functions-as-an-amine-oxidase
#17
Chankyu Jeong, Youngho Kim
Human lysyl oxidase-like 3 (LOXL3) functions as a copper-dependent amine oxidase toward collagen and elastin. The LOXL3 protein contains four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus in addition to the C-terminal characteristic domains of the lysyl oxidase (LOX) family, such as a copper-binding domain, a cytokine receptor‑like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a novel variant of LOXL3 (termed LOXL3-sv2), which lacked the sequences corresponding to exons 4 and 5 of LOXL3...
January 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28332555/loxl2-drives-epithelial-mesenchymal-transition-via-activation-of-ire1-xbp1-signalling-pathway
#18
Eva P Cuevas, Pilar Eraso, María J Mazón, Vanesa Santos, Gema Moreno-Bueno, Amparo Cano, Francisco Portillo
Epithelial-to-Mesenchymal Transition (EMT) is a key process contributing to the aggressiveness of cancer cells. EMT is triggered by activation of different transcription factors collectively known as EMT-TFs. Different cellular cues and cell signalling networks activate EMT at transcriptional and posttranscriptional level in different biological and pathological situations. Among them, overexpression of LOXL2 (lysyl oxidase-like 2) induces EMT independent of its catalytic activity. Remarkably, perinuclear/cytoplasmic accumulation of LOXL2 is a poor prognosis marker of squamous cell carcinomas and is associated to basal breast cancer metastasis by mechanisms no yet fully understood...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325283/silencing-of-carbohydrate-sulfotransferase-15-hinders-murine-pulmonary-fibrosis-development
#19
Yoshiro Kai, Koichi Tomoda, Hiroyuki Yoneyama, Masahiro Kitabatake, Atsuhiro Nakamura, Toshihiro Ito, Masanori Yoshikawa, Hiroshi Kimura
Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28257048/vanillin-suppresses-cell-motility-by-inhibiting-stat3-mediated-hif-1%C3%AE-mrna-expression-in-malignant-melanoma-cells
#20
Eun-Ji Park, Yoon-Mi Lee, Taek-In Oh, Byeong Mo Kim, Beong-Ou Lim, Ji-Hong Lim
Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR)...
March 1, 2017: International Journal of Molecular Sciences
keyword
keyword
9754
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"