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)

A specialized microenvironment or niche, which regulates maintenance, self-renewal, activation, and proliferation of stem cells by external signals, is one of the key prerequisites for stem cell function. However, the parameters determining the limbal stem cell niche are not yet defined. In order to characterize the role of basement membrane (BM) and extracellular matrix components in the generation of a microenvironmental niche for limbal stem and progenitor cells, we extensively analyzed the topographical variations of the BM zone of human ocular surface epithelia using immunohistochemistry and a large panel of antibodies to most of the presently described intrinsic and associated BM components. Apart from BM components uniformly expressed throughout all ocular surface epithelia (e.g. type IV collagen alpha5 and alpha6 chains, collagen types VII, XV, XVII, and XVIII, laminin-111, laminin-332, laminin chains alpha3, beta3,and gamma2, fibronectin, matrilin-2 and -4, and perlecan), the BM of the limbal epithelium shared many similarities with that of the conjunctival epithelium, including positive labelling for type IV collagen alpha1 and alpha2 chains, laminin alpha5, beta2, and gamma1 chains, nidogen-1 and -2, and thrombospondin-4, whereas type IV collagen alpha3, type V collagen, fibrillin-1 and -2, thrombospondin-1, and endostatin were present in the corneal BM, but lacking or more weakly expressed in the limbal and conjunctival BMs. As compared to both the corneal and conjunctival BMs, the limbal BM showed a markedly increased immunoreactivity for laminin alpha1, alpha2, beta1 chains, and agrin, and a specific but patchy immunoreactivity for laminin gamma3 chain, BM40/SPARC, and tenascin-C, which co-localized with ABCG2/p63/K19-positive and K3/Cx43/desmoglein/integrin-alpha2-negative cell clusters comprising putative stem and early progenitor cells in the basal epithelium of the limbal palisades. Components that were particularly expressed in the corneal-limbal transition zone included type XVI collagen, fibulin-2, tenascin-C/R, vitronectin, bamacan, chondroitin sulfate, and versican, all of which co-localized with vimentin-positive cell clusters comprising putative late progenitor cells in the basal epithelium. This pronounced heterogeneity of the BM in the limbal area, both in the region of limbal palisades and the corneal-limbal transition zone, appears to be involved in providing unique microenvironments for corneal epithelial stem and late progenitor cells. Identification of specific niche parameters might not only help to understand limbal stem cell regulation, but also to improve their selective enrichment and in vitro expansion for therapeutic strategies.
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PMID:Characterization of extracellular matrix components in the limbal epithelial stem cell compartment. 1792 80

Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. The compositions and functions of basement membranes have generally been well conserved throughout the subkingdom. Genetic analyses of basement membrane components in C. elegans have provided insights into their assembly and functions during development. Immuno- or GFP-tagged localization studies have shown that basement membranes on different tissues, or even sub-regions of tissues, contain different sets of proteins or alternatively spliced isoforms of them. Several components, including laminin, perlecan, type IV collagen and possibly osteonectin/SPARC, are essential for completion of embryogenesis, being necessary for tissue organization and structural integrity. In contrast, type XVIII collagen and nidogen are not required for viability but primarily influence organization of the nervous system. All of these proteins, with the exception of nidogen and the addition of fibulin, have roles of varying degree in morphogenesis of the gonad. A major family of cellular receptors for basement membrane proteins, the integrins, have also been characterized in C. elegans. As one might expect, integrins have been shown to function in many of the same processes as their potential ligands, the basement membrane components. While much remains to be explored, studies of basement membranes in C. elegans have been highly informative and hold great promise for improving our understanding of how these structures are assembled and how they function in development.
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PMID:Basement membranes. 1805 Apr 23

Cartilage is one of the very few naturally occurring avascular tissues where lack of angiogenesis is the guiding principle for its structure and function. This has attracted investigators who have sought to understand the biochemical basis for its avascular nature, hypothesising that it could be used in designing therapies for treating cancer and related malignancies in humans through antiangiogenic applications. Cartilage encompasses primarily a specialised extracellular matrix synthesised by chondrocytes that is both complex and unique as a result of the myriad molecules of which it is composed. Of these components, a few such as thrombospondin-1, chondromodulin-1, the type XVIII-derived endostatin, SPARC (secreted protein acidic and rich in cysteine) and the type II collagen-derived N-terminal propeptide (PIIBNP) have demonstrated antiangiogenic or antitumour properties in vitro and in vivo preclinical trials that involve several complicated mechanisms that are not completely understood. Thrombospondin-1, endostatin and the shark-cartilage-derived Neovastat preparation have also been investigated in human clinical trials to treat several different kinds of cancers, where, despite the tremendous success seen in preclinical trials, these molecules are yet to show success as anticancer agents. This review summarises the current state-of-the-art antiangiogenic characterisation of these molecules, highlights their most promising aspects and evaluates the future of these molecules in antiangiogenic applications.
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PMID:Antiangiogenic and anticancer molecules in cartilage. 2255 83