Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type XVIII collagen/endostatin is known to be crucial for the eye, as witnessed by severe eye defects in Knobloch syndrome patients with mutations in this collagen and in Col18a1(-/-) mice. We show here that in a specific C57BL background, 20% of the Col18a1(-/-) mice developed hydrocephalus, and dilation of the brain ventricles was observed by MRI in all of the mutant mice. Significant broadening was observed in the epithelial basement membrane (BM) of the choroid plexuses (CP), its width being 86.4+/-10.52 nm, compared with 61.4+/-6.05 nm in wild-type mice. The CP epithelial cell morphology was balloon-shaped rather than cuboidal, and the microvilli of the apical surface of the CP epithelium contained more vacuoles in the null mice than in the wild-type, as also did the CP epithelial cells, which is suggestive of alterations in cerebrospinal fluid production. Analysis of BMs elsewhere in the body revealed a broadened epidermal BM in the Col18a1(-/-) mice, but this did not result in any apparent functional deficiencies. Moreover, markedly broadened BMs were found in the atrioventricular valves of the heart and in the kidney tubules, whereas the glomerular mesangial matrix of the kidneys was expanded in the mutant mice and serum creatinine levels were elevated, indicating alterations in kidney filtration capacity. We thus suggest that type XVIII collagen is a structurally important constituent of BMs, and that its absence can result in a variety of phenotypic alterations.
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PMID:Structurally altered basement membranes and hydrocephalus in a type XVIII collagen deficient mouse line. 1525 16

Collagen XVIII is a component of basement membranes (BMs) with the structural properties of both a collagen and a proteoglycan. Proteolytic cleavage within its C-terminal domain releases a fragment, endostatin, which has been reported to have anti-angiogenesis effects. Molecular studies demonstrated binding of the endostatin domain to heparan sulfate and to BM components like laminin and perlecan, but the functional role of these interactions in vivo remains unknown. Insights into the physiological function of collagen XVIII/endostatin have recently been obtained through the identification of inactivating mutations in the human collagen XVIII/endostatin gene (COL18A1) in patients with Knobloch syndrome, characterized by age-dependent vitreoretinal degeneration and occipital encephalocele. That collagen XVIII/endostatin has an essential role in ocular development and the maintenance of visual function is further demonstrated by the ocular abnormalities seen in mice lacking collagen XVIII/endostatin. Age-dependent loss of vision in these mutant mice is associated with pathological accumulation of deposits under the retinal pigment epithelium, as seen in early stages of age-related macular degeneration in humans. In addition, recent evidence suggests that lack of collagen XVIII/endostatin predisposes to hydrocephalus formation. These recent findings demonstrate an important role for collagen XVIII/endostatin in cell-matrix interactions in certain tissues that may be compensated for in other tissues expressing this collagen.
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PMID:Physiological role of collagen XVIII and endostatin. 1585 86