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https://www.readbyqxmd.com/read/29627371/the-apparent-competitive-action-of-ecm-proteases-and-cross-linking-enzymes-during-fibrosis-applications-to-drug-discovery
#1
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
#2
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
#3
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
#4
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/29603864/vascular-smooth-muscle-cells-direct-extracellular-dysregulation-in-aortic-stiffening-of-hypertensive-rats
#5
Tristan T Hays, Ben Ma, Ning Zhou, Shaunrick Stoll, William J Pearce, Hongyu Qiu
Aortic stiffening is an independent risk factor that underlies cardiovascular morbidity in the elderly. We have previously shown that intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) play a key role in aortic stiffening in both aging and hypertension. Here, we test the hypothesis that VSMCs also contribute to aortic stiffening through their extracellular effects. Aortic stiffening was confirmed in spontaneously hypertensive rats (SHRs) vs. Wistar-Kyoto (WKY) rats in vivo by echocardiography and ex vivo by isometric force measurements in isolated de-endothelized aortic vessel segments...
March 30, 2018: Aging Cell
https://www.readbyqxmd.com/read/29600404/differential-gene-expression-of-extracellular-matrix-related-proteins-in-the-vaginal-apical-compartment-of-women-with-pelvic-organ-prolapse
#6
Haijiao Wang, Yukimi Kira, Akihiro Hamuro, Aki Takase, Daisuke Tachibana, Masayasu Koyama
INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a multifactorial disorder that impairs the quality of life (QoL) of older women in particular. The purpose of this study was to elucidate the pathogenesis of POP by focusing on the extracellular matrix (ECM). METHODS: Patients were classified into two groups-with or without cervical elongation-using the POP quantification system. Specimens were obtained from 29 women with POP during hysterectomy. The expression of fibulin-5, elastin, integrin β1 (ITGβ1), lysyl oxidase-like protein-1 (LOXL1) and collagen in the vagina, uterosacral ligament, and uterine cervix was investigated by quantitative real-time polymerase chain reaction (RT-PCR) and correlation between gene levels and severity of POP examined...
March 29, 2018: International Urogynecology Journal
https://www.readbyqxmd.com/read/29590645/pkc%C3%AE%C2%B5-increases-extracellular-elastin-and-fibulin-5-dance-in-dermal-fibroblasts
#7
Tomoyuki Nishizaki
BACKGROUND/AIMS: In the earlier study, the selective PKCε activator DCP-LA increased elastic fibres in the dermis of HR-1 hairless mice. As a process of elastic fibre formation, tropoelastin, an elastin monomer, is secreted into the extracellular space. Secreted tropoelastin is delivered to the microfibrils by fibulin-5/developmental arteries and neural crest epidermal growth factor-like (DANCE) and undergoes self-association. Then, tropoelastin assembles around the microfibrils, growing into elastin and elastic fibres by lysyl oxidase (LOX)- or LOX-like (LOXL)-mediated cross-linking...
March 23, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29581294/crystal-structure-of-human-lysyl-oxidase-like-2-hloxl2-in-a-precursor-state
#8
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/29579155/a-polymorphism-in-the-lysyl-oxidase-propeptide-domain-accelerates-carcinogen-induced-cancer
#9
Ana de la Cueva, Michael Emmerling, Sarah L Lim, Shi Yang, Philip C Trackman, Gail E Sonenshein, Kathrin H Kirsch
The propeptide (LOX-PP) domain of the lysyl oxidase proenzyme (Pro-LOX) was shown to inhibit the transformed phenotype of breast, lung and pancreatic cells in culture and the formation of Her2/neu-driven breast cancer in a xenograft model. A single nucleotide polymorphism (SNP, rs1800449) positioned in a highly conserved region of LOX-PP results in an Arg158Gln substitution (humans). This ArgGln substitution profoundly impaired the ability of LOX-PP to inhibit the invasive phenotype and xenograft tumor formation...
March 22, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29550472/pentagalloyl-glucose-increases-elastin-deposition-decreases-reactive-oxygen-species-and-matrix-metalloproteinase-activity-in-pulmonary-fibroblasts-under-inflammatory-conditions
#10
Vaideesh Parasaram, Nasim Nosoudi, Aniqa Chowdhury, Naren Vyavahare
mphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i...
March 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29549726/cav-1-deficiency-promotes-liver-fibrosis-in-carbon-tetrachloride-ccl-4-induced-mice-by-regulation-of-oxidative-stress-and-inflammation-responses
#11
De-Gang Ji, Yan Zhang, Song-Mei Yao, Xu-Jie Zhai, Li-Rong Zhang, Yao-Zhong Zhang, Hui Li
Caveolin-1 (Cav-1), as a membrane protein involved in the formation of caveolae, binds steroid receptors and endothelial nitric oxide synthase, limiting its translocation and activation. In the present study, we investigated the role of Cav-1 in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl4 ) in murine animals. Therefore, the wild type (WT) and Cav-1-knockout (Cav-1-/- ) mice were used in our study and subjected to CCl4 . The results indicated that CCl4 induced the decrease of Cav-1 expression in liver tissue samples...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29547702/inhibition-of-enzymes-involved-in-collagen-cross-linking-reduces-vascular-smooth-muscle-cell-calcification
#12
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/29547474/exfoliation-syndrome-a-disease-of-autophagy-and-loxl1-proteopathy
#13
Audrey M Bernstein, Robert Ritch, J Mario Wolosin
Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (XFM) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where XFM accumulations form on the surface of the ciliary body, iris and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies...
March 15, 2018: Journal of Glaucoma
https://www.readbyqxmd.com/read/29532123/collagen-xviii-and-loxl-4-polymorphisms-in-women-with-and-without-advanced-pelvic-organ-prolapse
#14
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
#15
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/29502979/amelioration-of-cavernosal-fibrosis-and-erectile-function-by-lysyl-oxidase-inhibition-in-a-rat-model-of-cavernous-nerve-injury
#16
Zhi-Hua Wan, Guo-Hao Li, Yong-Lian Guo, Wen-Zhou Li, Lin Chen, Yuan-Jie Zhang
BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or β-aminopropionitrile, a specific LOX activity inhibitor...
March 2018: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29498828/protein-derived-cofactors-revisited-empowering-amino-acid-residues-with-new-functions
#17
Victor L Davidson
A protein-derived cofactor is a catalytic or redox-active site in a protein that is formed by post-translational modification of one or more amino acid residues. These post-translational modifications are irreversible and endow the modified amino acid residues with new functional properties. This Perspective focusses on the following advances in this area that have occurred during recent years. The biosynthesis of the tryptophan tryptophylquinone (TTQ) cofactor is catalyzed by a di-heme enzyme, MauG. A bis-FeIV redox state of the hemes performs three two-electron oxidations of specific Trp residues via long-range electron transfer...
March 2, 2018: Biochemistry
https://www.readbyqxmd.com/read/29472856/silibinin-inhibits-nsclc-metastasis-by-targeting-the-egfr-lox-pathway
#18
Xiaoying Hou, Hongzhi Du, Xingping Quan, Lei Shi, Qianqian Zhang, Yao Wu, Yang Liu, Jing Xiao, Yong Li, Ligong Lu, Xun Ai, Meixiao Zhan, Shengtao Yuan, Li Sun
Tumor metastasis is the most lethal and debilitating process that threatens cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase (LOX) is an important contributor for tumor invasion, migration and the formation of the pre-metastatic niche. Although the relationship between LOX and poor prognosis of lung patients has been preliminary reported, the mechanism remains poorly understood. Here, we found that LOX overexpression is closely related to the survival of lung adenocarcinoma patients but not squamous cell carcinoma patients...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29470511/preliminary-analysis-of-proteome-alterations-in-non-aneurysmal-internal-mammary-artery-tissue-from-patients-with-abdominal-aortic-aneurysms
#19
Christina Lund Kidholm, Hans Christian Beck, Julie Bukh Madsen, Nikolai Bjødstrup Palstrøm, Jes Sanddal Lindholt, Lars Melholt Rasmussen
OBJECTIVE: The pathogenesis of abdominal aortic aneurysms (AAA) involves a disturbed balance of breakdown and buildup of arterial proteins. We envision that individuals with AAA carry generalized arterial protein alterations either because of effects of genetically or environmental AAA risk factors or because of compensatory changes due to signaling molecules released from the affected aneurysmal tissue. APPROACH: Protein extraction and quantitative proteome analysis by LC-MS/MS (liquid chromatography-mass spectrometry) was done on individual samples from the internal mammary artery from 11 individuals with AAA and 33 sex- and age-matched controls without AAA...
2018: PloS One
https://www.readbyqxmd.com/read/29467842/hypoxia-inducible-factor-1%C3%AE-regulates-epithelial-to-mesenchymal-transition-in-paraquat-induced-pulmonary-fibrosis-by-activating-lysyl-oxidase
#20
Jian Lu, Yongbing Qian, Wei Jin, Rui Tian, Yong Zhu, Jinfeng Wang, Xiaoxiao Meng, Ruilan Wang
Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced PF. In addition, hypoxia-inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF-1α- and LOX-mediated regulation of EMT remains unclear. The present study investigated the association between HIF-1α and LOX with regard to PQ-induced EMT...
March 2018: Experimental and Therapeutic Medicine
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