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lysyl oxidase

Leona Matsumoto, Yasushi Hirota, Tomoko Saito-Fujita, Norihiko Takeda, Tomoki Tanaka, Takehiro Hiraoka, Shun Akaeda, Hidetoshi Fujita, Ryoko Shimizu-Hirota, Shota Igaue, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Tomoyuki Fujii, Yutaka Osuga
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure...
June 18, 2018: Journal of Clinical Investigation
Sabrina M Peviani, Vinicius Guzzoni, Clara M Pinheiro-Dardis, Yara P da Silva, Alisson C R Fioravante, Adriana H Sagawa, Gabriel B Delfino, João L Q Durigan, Tania F Salvini
Stretching is a common method used to prevent muscle shortening and improve limited mobility. However, the effect of different time periods on stretching-induced adaptation of the extracellular matrix and its regulatory elements have yet to be investigated. We aimed to evaluate the expression of fibrillar collagens, sarcomerogenesis, metalloproteinase (MMP) activity and gene expression of the extracellular matrix (ECM) regulators in the soleus (SOL) muscle of rats submitted to different stretching periods. The soleus muscles were submitted to 10 sets of passive stretching over 10 (St 10d) or 15 days (St 15d) (1 min per set, with 30 seconds' rest between sets)...
June 13, 2018: Scientific Reports
Tohru Fukai, Masuko Ushio-Fukai, Jack H Kaplan
Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a co-factor in many physiological processes through Cu-containing enzymes, including mitochondrial energy production (via cytochrome c oxidase), protection against oxidative stress (via superoxide dismutase), and extracellular matrix stability (via lysyl oxidase). Since free Cu is potentially toxic, the bioavailability of intracellular Cu is tightly controlled by Cu transporters and Cu chaperones...
June 6, 2018: American Journal of Physiology. Cell Physiology
Jeremy D Eekhoff, Fei Fang, Spencer P Lake
The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding...
June 6, 2018: Connective Tissue Research
Patrina S P Poh, Verena Schmauss, Jacqui A McGovern, Daniel Schmauss, Mohit P Chhaya, Peter Foehr, Markus Seeger, Vasilis Ntziachristos, Dietmar W Hutmacher, Martijn van Griensven, Jan-Thorsten Schantz, Elizabeth R Balmayor
BACKGROUND: Capsular contracture is one of the most common complications in surgical interventions for aesthetic breast augmentation or post-mastectomy breast reconstruction involving the use of silicone prostheses. Although the precise cause of capsular contracture is yet unknown, the leading hypothesis is that it is caused by long-term unresolved foreign body reaction towards the silicone breast implant. To authors' best knowledge, this is the first study that elucidates the presence of lysyl oxidase (LOX)-an enzyme that is involved in collagen and elastin crosslinking within fibrous capsules harvested from patients with severe capsular contracture...
June 4, 2018: European Journal of Medical Research
T Gambichler, M Mahjurian-Namari, L Reininghaus, L Schmitz, M Skrygan, H-J Schulze, J Schaller, G Girolomoni
BACKGROUND: Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear. AIM: To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2. METHODS: We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs)...
May 29, 2018: Clinical and Experimental Dermatology
Ximao Cui, Guanghui Wang, Wenbin Shen, Zhenyu Huang, Hailan He, Long Cui
Colorectal cancer (CRC) is the third most common type of cancer. In the present study, the expression and intracellular localization of lysyl oxidase-like 2 (LOXL2) protein in CRC were examined. Quantitative polymerase chain reaction and western blot analysis of LOXL2 mRNA and protein expression was performed for 40 pairs of CRC tumor and normal mucosa tissue samples. The immunohistochemical staining of tissue microarrays was performed to detect LOXL2 protein expression. LOXL2 was highly expressed in the extracellular matrix and CRC cells...
May 21, 2018: Oncology Reports
Hong-Wei Wang, Peng Sun, Yao Chen, Li-Ping Jiang, Hui-Ping Wu, Wen Zhang, Feng Gao
Glaucoma is the leading cause of irreversible blindness globally. It is known that the incidence of glaucoma is closely associated with inheritance. A large number of studies have suggested that genetic factors are involved in the occurrence and development of glaucoma, and even affect the drug sensitivity and prognosis of glaucoma. In the present review, 22 loci of glaucoma are presented, including the relevant genes (myocilin, interleukin 20 receptor subunit B, optineurin, ankyrin repeat‑ and SOCS box‑containing protein 10, WD repeat‑containing protein 36, EGF‑containing fibulin‑like extracellular matrix protein 1, neurotrophin 4, TANK‑binding kinase 1, cytochrome P450 subfamily I polypeptide 1, latent transforming growth factor β binding protein 2 and TEK tyrosine kinase endothelial) and 74 other genes (including toll‑like receptor 4, sine oculis homeobox Drosophila homolog of 1, doublecortin‑like kinase 1, RE repeats‑encoding gene, retinitis pigmentosa GTPase regulator‑interacting protein, lysyl oxidase‑like protein 1, heat‑shock 70‑kDa protein 1A, baculoviral IAP repeat‑containing protein 6, 5,10‑methylenetetrahydrofolate reductase and nitric oxide synthase 3 and nanophthalmos 1) that are more closely associated with glaucoma...
May 23, 2018: Molecular Medicine Reports
Silvia Rosini, Nicholas Pugh, Arkadiusz M Bonna, David J S Hulmes, Richard W Farndale, Josephine C Adams
Fibrillar collagens of the extracellular matrix are critical for tissue structure and physiology; however, excessive or abnormal deposition of collagens is a defining feature of fibrosis. Regulatory mechanisms that act on collagen fibril assembly potentially offer new targets for antifibrotic treatments. Tissue weakening, altered collagen fibril morphologies, or both, are shared phenotypes of mice lacking matricellular thrombospondins. Thrombospondin-1 (TSP1) plays an indirect role in collagen homeostasis through interactions with matrix metalloproteinases and transforming growth factor-β1 (TGF-β1)...
May 29, 2018: Science Signaling
Benjamín Muñoz Calvo, Ana Villa Martínez, Susana López Orgil, Natalia López Andrés, Feliciano Román García, Virginia Víctor Palomares, Esther de la Calle de la Villa, Verónica Nadador Patiño, Ignacio Arribas-Gómez
INTRODUCTION AND OBJECTIVES: Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. METHODS: We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls...
May 25, 2018: Revista Española de Cardiología
Geovana Calvo-Anguiano, Jose J Lugo-Trampe, Alberto Camacho, Salvador Said-Fernández, Roberto Mercado-Hernández, Viviana Zomosa-Signoret, Augusto Rojas-Martínez, Rocio Ortiz-López
The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have in vitro models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated...
June 2018: Experimental and Therapeutic Medicine
Mohammad Faisal J Khan, Julian Little, Peter A Mossey, Régine Pm Steegers-Theunissen, Martina Bonsi, Rita Bassi Andreasi, Michele Rubini
To investigate possible association between functional common variants in the lysyl oxidase like 3 (LOXL3) gene and non-syndromic cleft palate (nsCP) we selected a common missense variant p.Ile615Phe (rs17010021), which was predicted to have a probably damaging effect on the LOXL3 enzyme. We genotyped 258 nsCP case-parent triads of European origin and tested genetic association using the transmission disequilibrium test (TDT) and log-linear regression analyses of genotypic relative risks (RR) and of parent-of-origin effects...
May 26, 2018: Congenital Anomalies
Aki Pui-Wah Tse, Karen Man-Fong Sze, Queenie Tsung-Kwan Shea, Elley Yung-Tuen Chiu, Felice Ho-Ching Tsang, David Kung-Chun Chiu, Misty Shuo Zhang, Derek Lee, Iris Ming-Jing Xu, Cerise Yuen-Ki Chan, Hui-Yu Koh, Chun-Ming Wong, Yong-Ping Zheng, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Hepatocellular carcinoma (HCC), accounting for 90% of primary liver cancer, is a lethal malignancy that is tightly associated with chronic hepatitis B virus (HBV) infection. HBV encodes a viral onco-protein, transactivator protein X (HBx), which interacts with proteins of hepatocytes to promote oncogenesis. Our current study focused on the interaction of HBx with a transcription factor, hypoxia-inducible factor-1α (HIF-1α), which is stabilized by low O2 condition (hypoxia) and is found to be frequently overexpressed in HCC intra-tumorally due to poor blood perfusion...
May 25, 2018: Oncogenesis
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
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
Leonie Rossow, Simona Veitl, Sandra Vorlová, Jacqueline K Wax, Anja E Kuhn, Verena Maltzahn, Berin Upcin, Franziska Karl, Helene Hoffmann, Sabine Gätzner, Matthias Kallius, Rajender Nandigama, Daniela Scheld, Ster Irmak, Sabine Herterich, Alma Zernecke, Süleyman Ergün, Erik Henke
The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease...
May 21, 2018: Oncogene
Elia C El Hajj, Milad C El Hajj, Van K Ninh, Jason D Gardner
The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Yoon Jin Cha, Woo Hee Jung, Ja Seung Koo
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Brian J Huang, Wendy E Brown, Thomas Keown, Jerry C Hu, Kyriacos A Athanasiou
Although numerous cartilage engineering methods have been described, few report generation of constructs greater than 4 cm2, which is the typical lesion size considered for cell-based therapies. Furthermore, current cell-based therapies only target focal lesions, while treatment of large non-isolated lesions remains an area of great demand. The objective of this study was to scale-up fabrication of self-assembled neocartilage from standard sizes of 0.2 cm2 to greater than 8 cm2. Passaged sheep articular chondrocytes were self-assembled into 5 mm or 25 mm dia...
May 16, 2018: Tissue Engineering. Part A
Yun Liu, Guanghui Wang, Zhonglin Liang, Zubing Mei, Tingyu Wu, Ang Cui, Chenying Liu, Long Cui
BACKGROUND: Colorectal cancer (CRC) is a common and lethal disease in which distant metastasis remains the primary cause of death. Paradoxical roles of LOX have been reported in CRC, and the intracellular function of LOX has also recently been determined. Correlations of LOX expression and its intracellular localization with clinicopathological features in CRC patients remain largely unknown. The aim of the present study was to explore the potential roles of LOX in CRC. METHODS: LOX messenger RNA expression was assayed by quantitative PCR in eight paired normal mucosa and tumor tissues...
May 15, 2018: Thoracic Cancer
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