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)

The initial migration of motor growth cones from the spinal cord into the periphery requires extrinsic cues, yet their identities are largely unknown. In zebrafish diwanka mutants, motor growth cones are motile but fail to pioneer into the periphery. Here, we report on the positional cloning of diwanka and show that it encodes LH3, a myotomally expressed multifunctional enzyme with lysyl hydroxylase and glycosyltransferase domains. Cloning, expression analysis, and ubiquitous overexpression of other LH family members reveals that only diwanka (lh3) possesses a critical role in growth cone migration. We show that this unique role depends critically on the LH3 glycosyltransferase domain, and provide compelling evidence that diwanka (lh3) acts through myotomal type XVIII collagen, a ligand for neural-receptor protein tyrosine phosphatases that guide motor axons. Together, our results provide the first genetic evidence that glycosyltransferase modifications of the ECM play a critical role during vertebrate motor axon migration.
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PMID:The myotomal diwanka (lh3) glycosyltransferase and type XVIII collagen are critical for motor growth cone migration. 1673 8

Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence forming another his-tag structure, was approved by the State Food and Drug Administration of China (SFDA) in 2005 for the treatment of non-small-cell lung cancer. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we examined the anti-invasive activities of endostar in vitro. The results showed that endostar suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a concentration-dependent manner. It could inhibit the wound healing migration of MDA-MB-435 cells and invasion of MDA-MB-435 cells through reconstituted ECM (matrigel). Zymography revealed that endostar decreased the secretion of MMP-2 and MMP-9. Endostar could also inhibit the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells. Additionally, endostar exerted an inhibitory effect on the phosphorylation of ERK1/2. Collectively, these data provided a molecular basis for the anti-invasive effects of endostar.
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PMID:Endostar suppresses invasion through downregulating the expression of matrix metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells. 1848 Apr 15

In the last fifteen years different extracellular matrix proteins and cleavage products have been identified. These molecules possess the ability to regulate vascular development, repair and function. However, the concept is still inconsistent and only partially understood. In this review, we will focus on angiogenesis regulation by extracellular matrix processing. Therefore, possible regulatory mechanisms in vascular biology controlled by different cleavage products of basement membrane proteins (e.g. endostatin and tumstatin, endorepellin), their activation by proteases and inhibitors, such as matrix metalloproteases (MMPs), cathepsins, tissue inhibitors of MMPs and cystatin, will be reviewed. Up to now there is only limited knowledge about the situations, under which different ECM cleavage products will be released and produced by proteases. Beside vascular growth and the formation of new blood vessels, it is also important to pay attention to the implication of the mentioned proteins in the vascular repair process. Physical exercise and its angio-regulatory potentials have become in the focus in recent years. We will therefore discuss physical exercise and its effects on the mentioned molecules regarding angiogenic inductions. Until today it remains to be clearly stated, which impact might be achieved by matrix cleavage products with respect to the regulation of vascular progenitor cells and their possible therapeutical role in support of vascular repair mechanisms. Furthermore, the current knowledge of the functional role of ECM in the vascular system is highlighted.
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PMID:Angiogenic and vascular modulation by extracellular matrix cleavage products. 1919 66

Mesalamine (5-aminosalicylate acid, 5-ASA) is an effective treatment for ulcerative colitis (UC). The mechanisms of its actions are not fully understood. Because angiogenesis is critical for healing UC, we examined whether 5-ASA alters the angiogenic balance between angiogenic factors [e.g., vascular endothelial growth factor (VEGF)] and antiangiogenic factors (e.g., endostatin and angiostatin) in the colon in experimental UC. Rats were treated with saline or 5-ASA (100 mg/kg) twice daily and euthanized 3 or 7 days after iodoacetamide-induced UC. Clinical signs (e.g., lethargy, diarrhea) and UC lesions were measured. Expression of VEGF, endostatin, angiostatin, tissue necrosis factor alpha (TNF-alpha), and matrix metalloproteinases (MMPs) 2 and 9 was determined by Western blots, enzyme-linked immunosorbent assay, and zymography in the distal colon. 5-ASA treatment reduced lethargy and diarrhea and significantly decreased colonic lesions (by approximately 50%) compared with saline treatment in UC (both, P < 0.05). 5-ASA did not reverse the increased levels of VEGF, but it significantly reduced expression of endostatin and angiostatin in UC compared with vehicle treatment (both, P < 0.05). Furthermore, 5-ASA treatment significantly diminished increased activity of TNF-alpha and MMP9 in UC. This is the first demonstration that 5-ASA treatment reverses an imbalance between the angiogenic factor VEGF and antiangiogenic factors endostatin and angiostatin in experimental UC. The effect of 5-ASA in UC may be caused by the down-regulation of expression of endostatin and angiostatin by modulation of MMP2 and MMP9 via inhibition of TNFalpha. The inhibition of antiangiogenic factors may represent a novel molecular mechanism of the therapeutic action of 5-ASA.
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PMID:Mesalamine restores angiogenic balance in experimental ulcerative colitis by reducing expression of endostatin and angiostatin: novel molecular mechanism for therapeutic action of mesalamine. 1976 47

Diabetic retinopathy is considered one of the vision-threatening diseases among working-age population. The pathogenesis of the disease is regarded multifactorial and complex: capillary basement membrane thickening, loss of pericytes, microaneuryms, loss of endothelial cells, blood retinal barrier breakdown and other anatomic lesions might contribute to macular edema and/or neovascularization the two major and sight threatening complications of diabetic retinopathy. A number of proangiogenic, angiogenic and antiangiogenic factors are involved in the pathogenesis and progression of diabetic retinal disease, Vascular Endothelial Growth Factor (VEGF) being one of the most important. Other growth factors, which are known to participate in the pathogenesis of the disease, are: Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Transforming Growth Factor (TGF), Placental Endothelial Cell Growth Factor (PlGF), Connective Tissue Growth Factor (CTGF). Other molecules that are involved in the disease mechanisms are: intergrins, angiopoietins, protein kinase C (PKC), ephrins, interleukins, leptin, angiotensin, monocyte chemotactic protein (MCP), vascular cell adhesion molecule (VCAM), tissue plasminogen activator (TPA), and extracellular matrix metalloproteinases (ECM-MMPs). However, the intraocular concentration of angiogenic factors is counterbalanced by the ocular synthesis of several antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, thrombospondin, steroids, atrial natriuretic peptide (ANP), inteferon, aptamer, monoclonal antibodies, VEGF receptor blocker, VEGF gene suppressors, intracellular signal transduction inhibitors, and extracellular matrix antagonists. Growth stimulation or inhibition by these factors depends on the state of development and differentiation of the target tissue. The mechanisms of angiogenesis factor action are very different and most factors are multipotential; they stimulate proliferation or differentiation of endothelial cells. This review attempts to briefly outline the knowledge about peptide growth factor involvement in diabetic retinopathy. Further ongoing research may provide better understanding of molecular mechanisms, disease pathogenesis and therapeutic interactions.
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PMID:Angiogenic growth factors and their inhibitors in diabetic retinopathy. 2059 64

We have set up an assay to study the interactions of live pathogens with their hosts by using protein and glycosaminoglycan arrays probed by surface plasmon resonance imaging. We have used this assay to characterize the interactions of Leishmania promastigotes with ~70 mammalian host biomolecules (extracellular proteins, glycosaminoglycans, growth factors, cell surface receptors). We have identified, in total, 27 new partners (23 proteins, 4 glycosaminoglycans) of procyclic promastigotes of six Leishmania species and 18 partners (15 proteins, 3 glycosaminoglycans) of three species of stationary-phase promastigotes for all the strains tested. The diversity of the interaction repertoires of Leishmania parasites reflects their dynamic and complex interplay with their mammalian hosts, which depends mostly on the species and strains of Leishmania. Stationary-phase Leishmania parasites target extracellular matrix proteins and glycosaminoglycans, which are highly connected in the extracellular interaction network. Heparin and heparan sulfate bind to most Leishmania strains tested, and 6-O-sulfate groups play a crucial role in these interactions. Numerous Leishmania strains bind to tropoelastin, and some strains are even able to degrade it. Several strains interact with collagen VI, which is expressed by macrophages. Most Leishmania promastigotes interact with several regulators of angiogenesis, including antiangiogenic factors (endostatin, anastellin) and proangiogenic factors (ECM-1, VEGF, and TEM8 [also known as anthrax toxin receptor 1]), which are regulated by hypoxia. Since hypoxia modulates the infection of macrophages by the parasites, these interactions might influence the infection of host cells by Leishmania.
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PMID:Large-scale investigation of Leishmania interaction networks with host extracellular matrix by surface plasmon resonance imaging. 2447 75

Background- Endostatin by virtue of their therapeutic value against rheumatoid arthritis have recently generated enormous interest among biomedical science. Recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. Objective- The main objective of the current manuscript is to enumerates the intrinsic role of endostatin in rheumatoid arthritis. Method- A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for preparation of the current article. Result- Endostatin is one such agent of subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear but it acts by downregulating or inhibiting the responses of various factors including Id1, Id3, matrix metalloproteinase and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance and hepatic steatosis. Conclusion-The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis and focus on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.
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PMID:Role Of Endostatin In Rheumatoid Arthritis. 3234 30