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

Abstract

Lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) are extracellular enzymes that deaminate peptidyl lysyl residues involved in the cross-linking of fibrillar collagens and elastin. While LOX is required for the survival of newborn mice, the role of LOXL during development remains unclear. Studies have shown that the same cell types express LOX and LOXL in the same tissues, but no functional differences have been established. We have compared the immunohistochemical localization of LOX and LOXL in various tissues from normal, young adult mice. LOX and LOXL were co-localized in the skin, aorta, heart, lung, liver and cartilage, but were localized to different areas in the kidney, stomach, small intestine, colon, retina, ovary, testis and brain. LOXL expression was further examined in tissues from different developmental stages. In embryonic mice (10.5-14.5 dpc), LOXL immunostaining was abundant in the heart, liver, intestine, and neural tube. LOXL was present in most major organs in late fetal (16.5 dpc) and newborn mice, but generally diminished as animals aged. Immunoreactivity was significantly reduced in the heart, lung, kidney and liver of 2 year-old mice, but remained prevalent in the skin and tongue. LOX and LOXL were also found in the nuclei of cells in a number of tissues. These results indicate that LOXL has a role during mouse development and in the maintenance of adult tissues.

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

“…[45] Lox has been shown to be quite important in cardiovascular development and function, especially related to the elastin layer in the aorta. [46], [47] This gene family is also important in cardiac remodeling. Up-regulation of Lox mRNA was also found in fibrotic myocardium distant from an infarct site in a mouse coronary artery ligation model.…”

New insights into elastic fiber assembly

“…LOX can cross-link recombinant tropoelastin in vitro without the presence of any other elastic fiber proteins (Bedell-Hogan et al, 1993). LOX localizes to the elastin/microfibril interface in aorta (Kagan et al, 1986) and LOX and LOXL1 colocalize in most elastic tissues (Hayashi et al, 2004). LOXL1 specifically localizes to sites of elastogenesis and interacts with fibulin-5 (Liu et al, 2004).…”

Intracellular localization of the matrix enzyme lysyl oxidase in polarized epithelial cells

“…LOX was detected using a rabbit polyclonal antibody against the N-terminus of the mature protein, seven amino acids down from the BMP-1 cleavage site (Li et al, 2004;Hayashi et al, 2004). Fibronectin expression was detected with a mouse monoclonal antibody (sc-18827, Santa Cruz Biotechnology) against the adhesive peptide FN CH/1 within the carboxy Hep II region.…”

“…Although epithelia face the extracellular matrix with their basal surfaces, there is poor knowledge about a potential role of LOX in epithelial cell types. A few reports however did provide evidence for LOX expression in some epithelial tissues based on immunohistochemistry data and one study detected LOX mRNA expression in cultured rabbit pigment epithelium cells (Omori et al, 2002, Hayashi et al, 2004, Noblesse et al, 2004Fogelgren et al, 2005). Additionally, recent findings indicate that LOX is a critical factor when breast epithelial tumor cells acquire a migratory and invasive phenotype in vitro (Kirschmann et al, 1999;Kirschmann et al, 2002;Payne et al, 2005).…”