Gene Symbol: Lox
Description: lysyl oxidase
Alias: H-rev142, Rrg1, protein-lysine 6-oxidase, Lysyl oxidase (an H-rev gene with its expression down-regulated in HRAS-transformed rat 208F fibroblasts)
Species: rat
Products:     Lox

Top Publications

  1. Lucero H, Ravid K, Grimsby J, Rich C, DiCamillo S, Maki J, et al. Lysyl oxidase oxidizes cell membrane proteins and enhances the chemotactic response of vascular smooth muscle cells. J Biol Chem. 2008;283:24103-17 pubmed publisher
    Lysyl oxidase (LOX) is a potent chemokine inducing the migration of varied cell types...
  2. Vora S, Palamakumbura A, Mitsi M, Guo Y, Pischon N, Nugent M, et al. Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of osteoblasts. J Biol Chem. 2010;285:7384-93 pubmed publisher
    Pro-lysyl oxidase is secreted as a 50-kDa proenzyme and is then cleaved to a 30-kDa mature enzyme (lysyl oxidase (LOX)) and an 18-kDa propeptide (lysyl oxidase propeptide (LOX-PP))...
  3. Khosravi R, Sodek K, Faibish M, Trackman P. Collagen advanced glycation inhibits its Discoidin Domain Receptor 2 (DDR2)-mediated induction of lysyl oxidase in osteoblasts. Bone. 2014;58:33-41 pubmed publisher
  4. Adam O, Theobald K, Lavall D, Grube M, Kroemer H, Ameling S, et al. Increased lysyl oxidase expression and collagen cross-linking during atrial fibrillation. J Mol Cell Cardiol. 2011;50:678-85 pubmed publisher
    ..RT-PCR and western Blot analysis revealed that LA of AF patients are characterized by increased lysyl oxidase (LOX) mRNA (218 ± 42%) and protein (253 ± 11%) expression...
  5. Bhaskar H, Udupa S, Udupa A. Effect of nifedipine and amlodipine on dead space wound healing in rats. Indian J Exp Biol. 2005;43:294-6 pubmed
    ..It is likely that the prohealing effects may be related to the improved antioxidant status too, since superoxide dismutase levels were observed to be higher in the CCB- treated animals. ..
  6. Chen L, Zhao Y, Gao S, Chou I, Toselli P, Stone P, et al. Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal lung fibroblasts treated with cigarette smoke condensate. Toxicol Sci. 2005;83:372-9 pubmed
    ..These results suggest that upregulation by CSC of cellular thiols may play an important role in the downregulation of LO and subsequently destabilization of the lung ECM in CS-induced emphysema. ..
  7. Chou D, Zhao Y, Gao S, Chou I, Toselli P, Stone P, et al. Perturbation of copper (Cu) homeostasis and expression of Cu-binding proteins in cadmium-resistant lung fibroblasts. Toxicol Sci. 2007;99:267-76 pubmed
    ..These results suggest that downregulation of LO is linked with upregulation of other Cu-binding proteins and with alteration in Cu homeostasis in the CdR phenotype. ..
  8. Maki J, Sormunen R, Lippo S, Kaarteenaho Wiik R, Soininen R, Myllyharju J. Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues. Am J Pathol. 2005;167:927-36 pubmed
    Lysyl oxidases, a family comprising LOX and four LOX-like enzymes, catalyze crosslinking of elastin and collagens...
  9. Macauley S, Tarnuzzer R, Schultz G, Chegini N, Oxford G, Humphreys Beher M. Extracellular-matrix gene expression during mouse submandibular gland development. Arch Oral Biol. 1997;42:443-54 pubmed

More Information


  1. Takahashi T, Friedmacher F, Takahashi H, Daniel Hofmann A, Puri P. Lysyl oxidase expression is decreased in the developing diaphragm and lungs of nitrofen-induced congenital diaphragmatic hernia. Eur J Pediatr Surg. 2015;25:15-9 pubmed publisher
    ..Lysyl oxidase (lox), an extracellular enzyme that catalyzes the cross-linking of ECM proteins, plays an essential role during ..
  2. Trackman P, Pratt A, Wolanski A, Tang S, Offner G, Troxler R, et al. Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted amino acid sequence. Biochemistry. 1990;29:4863-70 pubmed
    ..A 258-bp segment of the 3'-untranslated region of lysyl oxidase cDNA is 93% identical with a highly conserved region of the 3'-untranslated sequence of rat elastin cDNA.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Gao A, Sullivan K, Black L. Lysyl oxidase expression in cardiac fibroblasts is regulated by ?2?1 integrin interactions with the cellular microenvironment. Biochem Biophys Res Commun. 2016;475:70-5 pubmed publisher
    Lysyl oxidase (LOX) catalyzes crosslink formation between fibrillar collagens and elastins and an increase in LOX activity has been associated with cardiac fibrosis following myocardial infarction (MI)...
  4. Ooshima A, Midorikawa O. Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis. Jpn Circ J. 1977;41:1337-40 pubmed
  5. El Hajj E, El Hajj M, Ninh V, Bradley J, Claudino M, Gardner J. Detrimental role of lysyl oxidase in cardiac remodeling. J Mol Cell Cardiol. 2017;109:17-26 pubmed publisher
    ..matrix (ECM) remodeling, which is associated with increases in the collagen cross-linking enzyme, lysyl oxidase (LOX)...
  6. Bing Z, Linlin L, Jianguo Y, Shenshen R, Ruifang R, Xi Z. Effect of mechanical stretch on the expressions of elastin, LOX and Fibulin-5 in rat BMSCs with ligament fibroblasts co-culture. Mol Biol Rep. 2012;39:6077-85 pubmed publisher
    ..e. 6 and 12 days) induced more expression of elastin, LOX, and Fibulin-5, compared to the groups without stimulation...
  7. Smith Mungo L, Kagan H. PKC-MEK-MAPK-dependent signal transduction pathway mediates the stimulation of lysyl oxidase expression by serum and PDGF in rat aortic smooth muscle cells. J Cell Biochem. 2002;85:775-84 pubmed
    ..PDGF is shown to be the major component of fetal bovine serum, which stimulates the activity of a LO promoter construct. ..
  8. Thomassin L, Werneck C, Broekelmann T, Gleyzal C, Hornstra I, Mecham R, et al. The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem. 2005;280:42848-55 pubmed
    These studies were undertaken to determine how lysyl oxidase (LOX) and lysyl oxidase like-1 (LOXL) enzymes are targeted to their substrates in the extracellular matrix...
  9. Yang Z, Xiaohua W, Lei J, Ruoyun T, Mingxia X, Weichun H, et al. Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells. Am J Physiol Renal Physiol. 2010;299:F336-46 pubmed publisher
    ..Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups...
  10. Matsuura S, Mi R, Koupenova M, Eliades A, Patterson S, Toselli P, et al. Lysyl oxidase is associated with increased thrombosis and platelet reactivity. Blood. 2016;127:1493-501 pubmed publisher
    Lysyl oxidase (LOX) is overexpressed in various pathologies associated with thrombosis, such as arterial stenosis and myeloproliferative neoplasms (MPNs)...
  11. Tsuda T, Gao E, Evangelisti L, Markova D, Ma X, Chu M. Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes. Cardiovasc Res. 2003;59:926-33 pubmed
    ..Molecular and histopathological findings demonstrate that abnormal myocardial fibrosis can be induced by a small infarct independent of secondary hemodynamic changes. ..
  12. Nuthakki V, Fleser P, Malinzak L, Seymour M, Callahan R, Bendick P, et al. Lysyl oxidase expression in a rat model of arterial balloon injury. J Vasc Surg. 2004;40:123-9 pubmed
    ..Accumulation of extracellular matrix is a major factor in growth of the restenotic lesion, and modulation of lysyl oxidase activity may offer a therapeutic method for decreasing or preventing recurrent stenosis. ..
  13. Starcher B, Madaras J, Tepper A. Lysyl oxidase deficiency in lung and fibroblasts from mice with hereditary emphysema. Biochem Biophys Res Commun. 1977;78:706-12 pubmed
  14. Lau Y, Gobin A, West J. Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing. Ann Biomed Eng. 2006;34:1239-46 pubmed
    ..Addition of an inhibitor of LO abolished this increase. We applied this system in a rat dermal wound healing model and showed that treatment with LO-producing GAMs led to significantly enhanced mechanical strength of the wound site. ..
  15. Rodriguez C, Alcudia J, Martinez Gonzalez J, Raposo B, Navarro M, Badimon L. Lysyl oxidase (LOX) down-regulation by TNFalpha: a new mechanism underlying TNFalpha-induced endothelial dysfunction. Atherosclerosis. 2008;196:558-64 pubmed
    ..Down-regulation of lysyl oxidase (LOX), a key enzyme in extracellular matrix maturation, by pro-atherogenic risk factors such as LDL and homocysteine, is ..
  16. Behmoaras J, Slove S, Seve S, Vranckx R, Sommer P, Jacob M. Differential expression of lysyl oxidases LOXL1 and LOX during growth and aging suggests specific roles in elastin and collagen fiber remodeling in rat aorta. Rejuvenation Res. 2008;11:883-9 pubmed publisher
    ..a role for lysyl oxidase-like (LOXL1) in adult elastin synthesis and a role for its isoform, lysyl oxidase (LOX), in the synthesis of both collagens and elastin during development...
  17. Mello M, Alvarenga E, Vidal B, Di Donato A. Chromatin supraorganization, mitotic abnormalities and proliferation in cells with increased or down-regulated lox expression: Indirect evidence of a LOX-histone H1 interaction in vivo. Micron. 2011;42:8-16 pubmed publisher
    ..These enzymes are present inside the nuclei of certain mammalian cells. Previous studies have proposed LOX binding to histone H1 in vitro, and histone H1 is known to control global chromatin compaction and mitotic ..
  18. Khosravi R, Sodek K, Xu W, Bais M, Saxena D, Faibish M, et al. A novel function for lysyl oxidase in pluripotent mesenchymal cell proliferation and relevance to inflammation-associated osteopenia. PLoS ONE. 2014;9:e100669 pubmed publisher
  19. Kagan H, Li W. Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem. 2003;88:660-72 pubmed
    ..Recent studies have demonstrated that LO appears to function within the cell in a manner, which strongly modifies cellular activity. Newly discovered LO-like proteins also likely play unique roles in biology. ..
  20. Rowe D, McGoodwin E, Martin G, Grahn D. Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. J Biol Chem. 1977;252:939-42 pubmed
    ..An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals. ..
  21. Vivoli G, Bergomi M, Rovesti S, Pinotti M, Caselgrandi E. Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension. Biol Trace Elem Res. 1995;49:97-106 pubmed
    ..alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated...
  22. Herrera V, Didishvili T, Lopez L, Ruiz Opazo N. Differential regulation of functional gene clusters in overt coronary artery disease in a transgenic atherosclerosis-hypertensive rat model. Mol Med. 2002;8:367-75 pubmed
    ..Although more studies are necessary, early concordance with current pathogenic paradigms of human coronary plaque destabilization and post-ischemic myocardial response provides translational significance to observations and hypotheses. ..
  23. LI P, He Q, Cao T, Yong G, Szauter K, Fong K, et al. Up-regulation and altered distribution of lysyl oxidase in the central nervous system of mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Brain Res Mol Brain Res. 2004;120:115-22 pubmed
    ..Lysyl oxidase (LOX) is one of the genes that are known to be up-regulated in ALS patients...
  24. Hurtado P, Vora S, Sume S, Yang D, St Hilaire C, Guo Y, et al. Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation. Biochem Biophys Res Commun. 2008;366:156-61 pubmed
    ..The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map ..
  25. Giampuzzi M, Oleggini R, Di Donato A. Altered adhesion features and signal transduction in NRK-49F cells transformed by down-regulation of lysyl oxidase. Biochim Biophys Acta. 2003;1647:239-44 pubmed
    Lysyl oxidase (LOX) down-regulation induced an oncogenic phenotype in NRK-49F...
  26. Zhao Y, Gao S, Chou I, Toselli P, Stone P, Li W. Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts. Toxicol Sci. 2006;90:478-89 pubmed
  27. Nilsson M, Adamo H, Bergh A, Halin Bergström S. Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer. Sci Rep. 2016;6:19608 pubmed publisher
    Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects...
  28. Maki J, Rasanen J, Tikkanen H, Sormunen R, Mäkikallio K, Kivirikko K, et al. Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Circulation. 2002;106:2503-9 pubmed
    ..We studied the role of the first described isoenzyme Lox by inactivating its gene in mice. Murine Lox gene was disrupted by routine methods...
  29. Martínez Martínez E, Rodríguez C, Galán M, Miana M, Jurado López R, Bartolomé M, et al. The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats. J Mol Cell Cardiol. 2016;92:96-104 pubmed publisher
    Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system...
  30. Wang J, Zhu Y, Tan J, Meng X, Xie H, Wang R. Lysyl oxidase promotes epithelial-to-mesenchymal transition during paraquat-induced pulmonary fibrosis. Mol Biosyst. 2016;12:499-507 pubmed publisher
    Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays a critical role in pulmonary fibrosis...
  31. Voloshenyuk T, Landesman E, Khoutorova E, Hart A, Gardner J. Induction of cardiac fibroblast lysyl oxidase by TGF-?1 requires PI3K/Akt, Smad3, and MAPK signaling. Cytokine. 2011;55:90-7 pubmed publisher
    Lysyl oxidase (LOX) is a key extracellular enzyme responsible for the post-translational modification of collagens I and III to form mature fibrillar collagen...
  32. Sinha A, Nosoudi N, Vyavahare N. Elasto-regenerative properties of polyphenols. Biochem Biophys Res Commun. 2014;444:205-11 pubmed publisher
    ..to monomeric tropoelastin and enhance coacervation, aid in crosslinking of elastin by increasing lysyl oxidase (LOX) synthesis, and by blocking MMP-2 activity...
  33. Voloshenyuk T, Hart A, Khoutorova E, Gardner J. TNF-? increases cardiac fibroblast lysyl oxidase expression through TGF-? and PI3Kinase signaling pathways. Biochem Biophys Res Commun. 2011;413:370-5 pubmed publisher
    ..Lysyl oxidase (LOX) is a key enzyme responsible for the maturation of extracellular matrix proteins, including collagens type I and ..
  34. Trackman P, Pratt A, Wolanski A, Tang S, Offner G, Troxler R, et al. Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted amino acid sequence. Biochemistry. 1991;30:8282 pubmed
  35. Lee V, Halabi C, Hoffman E, Carmichael N, Leshchiner I, Lian C, et al. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci U S A. 2016;113:8759-64 pubmed publisher
    ..whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family...
  36. Xiao X, Ren J, Chen J, Liu Z, Tian Y, Nabar N, et al. LOX-related collagen crosslink changes act as an initiator of bone fragility in a ZDF rats model. Biochem Biophys Res Commun. 2018;495:821-827 pubmed publisher
    ..surface morphology, pre- and post-yield bone mechanical behavior, insoluble collagen volume, lysyl oxidase family (LOX) enzyme levels and correlation analysis was performed to determine the relationship between insoluble collagen and ..
  37. Rodriguez M, Pascual G, Cifuentes A, Pérez Kohler B, Bellon J, Bujan J. Role of lysyl oxidases in neointima development in vascular allografts. J Vasc Res. 2011;48:43-51 pubmed publisher
    Extracellular matrix deposition is the main factor inducing stenotic lesions in arterial grafts. Lysyl oxidases (LOX) play a key role in stabilizing collagen and elastin...
  38. Vora S, Guo Y, Stephens D, Salih E, Vu E, Kirsch K, et al. Characterization of recombinant lysyl oxidase propeptide. Biochemistry. 2010;49:2962-72 pubmed publisher
    ..In addition, lysyl oxidase has tumor suppressor activity that has been shown to depend on the propeptide region (LOX-PP) derived from pro-lysyl oxidase (Pro-LOX) and not on lysyl oxidase enzyme activity...
  39. Harlow C, Rae M, Davidson L, Trackman P, Hillier S. Lysyl oxidase gene expression and enzyme activity in the rat ovary: regulation by follicle-stimulating hormone, androgen, and transforming growth factor-beta superfamily members in vitro. Endocrinology. 2003;144:154-62 pubmed
    Lysyl oxidase (LOX) catalyzes the final enzymatic reaction required for cross-linking of collagen and elastin fibers and therefore has a crucial role in regulating the formation and maintenance of extracellular matrix in the ovary...
  40. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB. Arterioscler Thromb Vasc Biol. 2009;29:1080-6 pubmed publisher
    ..RT-PCR and immunohistochemistry showed reduced expression of procollagen type I, III, and lysyl oxidase (LOX) in CA walls. Treatment with the LOX inhibitor beta-aminopropionitrile resulted in enhanced progression of CA...
  41. Descamps O, Riondel J, Ducros V, Roussel A. Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech Ageing Dev. 2005;126:1185-91 pubmed
    ..Our results suggest that alternate fasting could exert a beneficial antioxidant effect and a modulation of the oxidative stress associated with aging. ..
  42. Sommer P, Gleyzal C, Raccurt M, Delbourg M, Serrar M, Joazeiro P, et al. Transient expression of lysyl oxidase by liver myofibroblasts in murine schistosomiasis. Lab Invest. 1993;69:460-70 pubmed
    ..Myofibroblasts are involved in the expression of the lysyl oxidase which may be secreted as a proenzyme and an activated enzyme. ..
  43. Kemppainen R, Hamalainen E, Kuivaniemi H, Tromp G, Pihlajaniemi T, Kivirikko K. Expression of mRNAs for lysyl oxidase and type III procollagen in cultured fibroblasts from patients with the Menkes and occipital horn syndromes as determined by quantitative polymerase chain reaction. Arch Biochem Biophys. 1996;328:101-6 pubmed
    ..The present and previous data indicate that the Menkes syndrome may involve several abnormalities in the expression of genes for connective tissue proteins. ..
  44. Li S, Yang X, Li W, Li J, Su X, Chen L, et al. N-acetylcysteine downregulation of lysyl oxidase activity alleviating bleomycin-induced pulmonary fibrosis in rats. Respiration. 2012;84:509-17 pubmed publisher
    ..previous findings showing elevation of glutathione (GSH) content associated with downregulation of lysyl oxidase (LOX) activity, which is essential for collagen deposition, the aim of the present study was to test the hypothesis that ..
  45. Zhang Y, Ghazwani M, Li J, Sun M, Stolz D, He F, et al. MiR-29b inhibits collagen maturation in hepatic stellate cells through down-regulating the expression of HSP47 and lysyl oxidase. Biochem Biophys Res Commun. 2014;446:940-4 pubmed publisher
    ..Heat shock protein 47 (HSP47) and lysyl oxidase (LOX) are known to be essential for ECM maturation...
  46. Huffman M, Curci J, Moore G, Kerns D, Starcher B, Thompson R. Functional importance of connective tissue repair during the development of experimental abdominal aortic aneurysms. Surgery. 2000;128:429-38 pubmed
    ..In contrast, reducing the proteolytic destruction of connective tissue proteins promotes stabilization of the aneurysmal aorta. ..
  47. Nellaiappan K, Risitano A, Liu G, Nicklas G, Kagan H. Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. J Cell Biochem. 2000;79:576-82 pubmed
    ..Thus, once secreted and proteolytically processed, mature LO can enter the cells and concentrate within nuclei in a manner that appears to be specific and independent of its catalytic activity. ..
  48. Trackman P, Feres Filho E, Choi Y. The 3'-untranslated region of rat lysyl oxidase cDNA. Biochim Biophys Acta. 1995;1260:355-60 pubmed
    ..We conclude that the elastin-like sequence previously reported in rat lysyl oxidase cDNA is not a species-specific sequence, and most probably resulted from spurious ligation reactions during construction of the cDNA library. ..
  49. Onoda M, Yoshimura K, Aoki H, Ikeda Y, Morikage N, Furutani A, et al. Lysyl oxidase resolves inflammation by reducing monocyte chemoattractant protein-1 in abdominal aortic aneurysm. Atherosclerosis. 2010;208:366-9 pubmed publisher
    Lysyl oxidase (LOX) is an enzyme critical for the stability of extracellular matrix and also known to have diverse biological functions. Little is known, however, about the role of LOX in regulating inflammation...