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Physiological role of collagen XVIII and endostatin
Author(s) -
Marneros Alexander G.,
Olsen Bjorn R.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2134rev
Subject(s) - endostatin , perlecan , basement membrane , extracellular matrix , microbiology and biotechnology , angiogenesis , mmp2 , chemistry , retinal pigment epithelium , angiogenesis inhibitor , laminin , retinal , pathology , proteoglycan , biology , biochemistry , cancer research , medicine , gene , downregulation and upregulation
ABSTRACT 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.—Marneros, A. G., Olsen, B. R. Physiological role of collagen XVIII and endostatin. FASEB J . 19, 716–728 (2005)