Increased expression of lysyl oxidase in skin with scleroderma

Abstract

Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the formation of a lysinederived aldehyde. In order to study cross-linking in scleroderma. we used monoclonal antibodies to lysyl oxidase to determine the localization of this enzyme in systemic and loctilized scleroderma. and compared the distributions obtained with that in normal skin. Using an indirect immunofluorescent antibody method and an avidin-biotinylated enzyme complex method. 11 cases of diffuse type of systemic scleroderma and seven cases of localized scleroderma were studied. In the oedematous stage of systemic scleroderma. intracellular and extracellular lysyl oxidase were remarkably increased in the dermis. particularly in groups around blood vessels. In the sclerotic stage of systemic scleroderma. lysyl oxidase was detected intracellularly in fihrohlasts and extracellularly among collagen bundles between the lower dermis and the subcutaneous tat tissue. In localized scleroderma, a marked increase in lysyl oxidase was observed in mononuclear cells and fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat tissue, in addition to the extracellular deposits between collagen bundles. The increase in lysyl oxidase in localized scleroderma was much more common than in the oedemalous stage of systemic scleroderma. These findings indicated that intraceliular and extracellular expression of lysyl oxidase expression was greater in sclerodermatous skin than in normal skin.

Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues

“…Antibodies generated against LOX have been localized to amorphous elastin and collagen fibers (Kagan et al 1986, Baccarani-Contri et al 1989). An increase in LOX immunoreactivity has been correlated with an increase in collagen deposition during tissue fibrosis (Chanoki et al 1995, Di Donato et al 1997, Kim et al 1999, Streichenberger et al 2001. Increases in LOX activity was also correlated with the increase of collagen expression in vitro (Feres-Filho et al 1995) and in vivo (Quaglino et al 1993).…”

Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension

“…Remodelling of the heart due to persistent elevations of ventricular developed pressure leads to changes in the amount of collagen, collagen phenotype and collagen cross-linking [26]. Cross-linking has not been investigated in the hearts of SSc patients, but is increased in skin with SSc [27,28]. It may be speculated that SSc myocardial tissue expresses an increased degree of collagen cross-linking that contributes to an impaired cardiac contractility.…”

Lysyl oxidase in colorectal cancer

“…Thus far, it appears that LOX alone is critically important in development but that LOXL1 and likely the other family members are vital for the maintenance of normal tissue homeostasis. This is further reinforced by many publications in which abnormal LOX expression or activity is associated with a wide spectrum of human pathological states including scleroderma (11), Menkes disease, Ehler-Danlos syndrome (61), occipital horn syndrome (10,38), lung and liver fibrosis (14), and liver cirrhosis (31), as well as in many cancers (reviewed in Ref. 7).…”