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

Corneal neovascularization (CNV) associated with severe limbal stem cell (LSC) deficiency remains a challenging ocular surface disease in that corneal inflammation may persist and progress, and the condition will not improve without LSC transplantation. A prominent feature after successful LSC transplantation is the suppression of corneal inflammation and CNV, which is generally attributed to the endogenous anti-angiogenic/anti-inflammatory factors secreted by corneal epithelial cells. In addition, corneal epithelial basement membrane (EBM) plays a unique role in the regulation of angiogenesis; several potent anti-angiogenic factors are derived from the matrix component of EBM, such as endostatin (from collagen XVIII) and restin (from collagen XV). Also, angio-inhibitory thrombospondin and tissue inhibitor of metalloproteinase-3 are deposited in EBM. Moreover, the heparan sulphate proteoglycan in EBM can bind and sequester VEGF and FGF-2 from activation. Recently, cultivated corneal epithelial transplantation (CCET) and cultivated oral mucosal epithelial transplantation (COMET) have emerged as promising techniques for the treatment of LSC deficiency. When human limbo-corneal epithelial (HLE) cells are cultivated on cryopreserved amniotic membrane, production of endostatin, restin, and IL-1ra is enhanced. This highlights the significance of delicate epithelial-matrix interactions in the generation of anti-angiogenic/anti-inflammatory factors by HLE cells, and this may, in part, explain the rapid restoration of corneal avascularity following CCET. In addition, whether epithelial stem cells can persist after transplantation is the key for CCET and COMET. Emerging evidence of long-term survival of cultivated epithelial cells after transplantation suggest that epithelial stem cells can be isolated and cultivated in vitro, and can re-establish the epithelial phenotype in vivo. Taken together, the merits of enhanced anti-angiogenic activity and the preservation of corneal epithelial stem cells encourage further application of this tissue engineering technique for ocular surface reconstruction.
 ...
PMID:Matrix revolution: molecular mechanism for inflammatory corneal neovascularization and restoration of corneal avascularity by epithelial stem cell transplantation. 1963 46

Collagen XVIII is a heparan sulphate proteoglycan which is expressed ubiquitously in different basement membranes throughout the body. Its C-terminal fragment, endostatin, has been found to inhibit angiogenesis and tumor growth by restricting endothelial proliferation and migration and inducing apoptosis of endothelial cells. Collagen XVIII has three variants, of which the shortest one is found in most vascular and epithelial BM structures, whereas the longer variants are found especially in the liver. The longest or frizzled variant has a cysteine-rich domain in its N-terminus that has been shown to inhibit Wnt signaling in vitro. The presence of collagen XVIII homologues in organisms such as C. elegans, Xenopus laevis, zebrafish and chick suggests a fundamental role for this BM collagen. Mutations in the collagen XVIII gene lead to the Knobloch syndrome, which is characterized by high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele. Mice lacking collagen XVIII also show several ocular abnormalities. This suggests that in physiological conditions collagen XVIII is mostly needed for the proper development of the eye. Moreover, it appears to be needed for the structural stability of basement membranes in several other organs, and increasing evidence shows its importance for other organs in non-physiological situations such as atherosclerosis, glomerulonephritis or other type of tissue damage. This review focuses on clarifying the roles of collagen XVIII and its variants and domains in various physiological and pathological conditions.
 ...
PMID:The multiple functions of collagen XVIII in development and disease. 2116 48