elastin and Cleft-Palate

Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.

Topics: Amino Acid Oxidoreductases; Arthritis; Cleft Palate; Collagen; Connective Tissue Diseases; Elastin; Epithelial-Mesenchymal Transition; Extracellular Matrix; Gene Expression Regulation; Hearing Loss, Sensorineural; Humans; Isoenzymes; Myopia; Neoplasms; Organ Specificity; Retinal Detachment; Signal Transduction; Snail Family Transcription Factors; STAT3 Transcription Factor

Topics: Abnormalities, Drug-Induced; Amino Acid Oxidoreductases; Aminopropionitrile; Aneurysm; Animals; Aortic Aneurysm; Blood Vessels; Bone and Bones; Bone Diseases; Cleft Palate; Collagen; Connective Tissue; Elastin; Fetus; Heart Defects, Congenital; Humans; Kyphosis; Lathyrism; Lysine; Neurologic Manifestations; Nitriles; Poultry Diseases; Rodent Diseases; Spinal Cord; Spinal Cord Diseases; Stomach; Turkeys

Topics: Abnormalities, Multiple; Beckwith-Wiedemann Syndrome; Child, Preschool; Chromosome Duplication; Chromosomes, Human, Pair 11; Cleft Lip; Cleft Palate; Costello Syndrome; Cutis Laxa; Elastin; Female; Humans; Hydrocephalus; Karyotype; Proto-Oncogene Proteins p21(ras)

Topics: Abnormalities, Multiple; Calcium-Binding Proteins; Child; Child, Preschool; Cleft Palate; Contractile Proteins; Cutis Laxa; Elastin; Extracellular Matrix Proteins; Face; Family Health; Fatal Outcome; Female; Genetic Linkage; Haplotypes; Humans; Infant; Infant, Newborn; Intellectual Disability; Male; Microsatellite Repeats; Pedigree; Protein-Lysine 6-Oxidase; Skin; Syndrome

The density of elastin in the intermediate portion between the lateral lamina and the medial lamina of human eustachian tube (ET) cartilage was examined in six normal adults, seven normal children, and six children with cleft palate (CP) in order to obtain information about how the physical properties of the ET cartilage differ as a function of age and presence of CP. Cross sections of the midcartilaginous portions of the ETs that had been stained with Weigert's elastin stain were photographed at uniform magnification, the area for study was projected, and the meshlike are of the ET cartilage that stained elastin-positive was represented on paper by lines. A digitizer was used to measure the total length of all the lines representing elastin in each photomicrograph, and the mean was determined for each of the three groups. The mean density of elastin was significantly greater in normal adults than in normal children (Student's t test, t = 2.781; p less than .02). It was also significantly greater in normal children than in CP children (Wilcoxon t = 24.0; p less than .05). These results appear to indicate that CP children have poorer elasticity in this area of the ET cartilage, which might cause functional obstruction (floppiness) of the ET in those children.

Topics: Adult; Aging; Cartilage; Child, Preschool; Cleft Palate; Elastin; Eustachian Tube; Histocytochemistry; Humans; Infant; Infant, Newborn; Middle Aged; Reference Values