Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability to discriminate reliably at the histological level between blood and lymphatic microcapillaries would greatly assist the study of a number of biological and pathological questions and may also be of clinical utility. A structure-function comparison of these types of microcapillary suggests that differences which could function as markers to allow discrimination between blood and lymphatic endothelium should exist. Indeed, to date a variety of such markers have been proposed, including basement membrane components, constituents of junctional complexes such as desmoplakin and enzymes such as 5'-nucleotidase. Additionally, a variety of cell surface molecules are thought to be differentially expressed, including PAL-E, VEGFR-3, podoplanin, and LYVE-1. Several of the lymphatic markers proposed in the literature require further characterization to demonstrate fully their lymphatic specificity and some have proven not to be reliable. The relative merits and drawbacks of each of the proposed markers is discussed.
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PMID:Markers for the lymphatic endothelium: in search of the holy grail? 1159 51

A family of growth factors highly specific for endothelial cells was identified more than 10 years ago, in which the receptor of vascular endothelial growth factor C (VEGFR-3) is implicated in the regulation of lymphatic development and regeneration. Comparative studies on the lymphatic network and lymphangiogenesis have been done mainly using combined 5'-nucleotidase (5'-Nase) enzyme and VEGFR-3 immunohistochemical approaches in adult and fetal gastric walls. Developing lymphatic networks represented fewer blind ends and branches than mature networks in whole-mount preparations. Many circular lymphatic-like structures exhibited VEGFR-3 expression and weak 5'-Nase activity in the early embryonic stage, showing visible morphological properties in the lymphatic endothelium. These newly formed lymphatics showed an obvious accumulation in the submucosa and serosa and a variation in the intensity of VEGFR-3 binding to endothelial cells among samples. A reaction product for anti-VEGFR-3 was found on the luminal surface of endothelial cells and on the membrane of some organelles and intraluminal lymphocytes. These findings indicate that an active proliferating feature of the clustered developing lymphatics may create a favorable environment for their sprouting and growth, which may serve as a functional requirement for lymph drainage in the region.
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PMID:Lymphatic network and lymphangiogenesis in the gastric wall. 1258 61

Lymphatic spread of colorectal cancer cells to regional lymph nodes is one of the early events in metastatic cancer, and is often associated with distant metastatic spread and a poor prognosis. This study examined lymphangiogenic factors, and in particular a panel of newly discovered lymphangiogenic markers, in colorectal cancer tissues from a cohort of patients. Paired samples (background normal mucosa and cancer) of colon tissue were obtained from patients with colorectal cancer. The expression and levels of the VEGF-C and VEGF-D cytokines, the VEGF receptors VEGFR-2 and VEGFR-3, and newly described lymphatic endothelial markers, LYVE-1, Prox-1, podoplanin and 5'-nucleotidase were assessed. RNA was extracted from the frozen colon tissues. The level of expression for each factor/marker was determined using RT-PCR and quantified using a real-time quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as internal standards. VEGF-D was expressed to a significantly higher degree in the colon tumour tissues. There was no significant difference between the expression levels for both VEGF-C and its receptor, VEGFR-2, in background and cancer tissues. However, levels of the VEGFR-3 receptor were found to be significantly higher in colon cancer than the normal background tissues. LYVE-1 levels were below detection in most cases. There was a significant increase in the degree of Prox-1 and 5'-nucleotidase expression in colon cancer tissue. Podoplanin expression was also increased in the cancer samples. These markers indicate an increase in lymphangiogenesis in colon cancer, and may therefore have prognostic value for colon cancer patients.
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PMID:Quantitative analysis of lymphangiogenic markers in human colorectal cancer. 1285 6

Regeneration of lymphatic vessels after transection of the muscle coat in the rat jejunum was studied by histochemical methods. The lymphatic regrowth occurred behind the regeneration of blood vessels. Enzyme histochemistry for 5'-nucleotidase (5'-Nase) demonstrated the manner of lymphatic regrowth, which was essentially attributed to vascular sprouting from preexisting lymphatics, and structural changes of the endothelial cells indicating their high migratory potential. The lymphatic regeneration progressively advanced with vascular maturation throughout the experimental period. The expression of 5'-Nase in the regenerating lymphatics was increased in proportion to their growth. VEGF-C, a highly specific lymphangiogenic factor, was highly expressed in a subpopulation of interstitial cells, being close to the regrowing lymphatics with immunoreactivity of its receptor, VEGFR-3, in the regenerative area. The present findings suggest that transection of the intestinal muscle coat affords a useful experimental model for the investigation of lymphatic regeneration in tissue repair and that the interstitium may play a crucial role in lymphangiogenesis.
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PMID:Regrowth of lymphatic vessels following transection of the muscle coat in the rat small intestine. 1506 37

The vascular endothelial growth factor-C (VEGF-C), a specific lymphangiogenic growth factor, raises new questions and perspectives in studying lymphatic development and regeneration. Wound healing skins in mice were processed for 5'-nucleotidase (5'-Nase) and VEGFR-3 (the receptor of VEGF-C) histochemical staining to distinguish lymphatics from blood capillaries and to analyze lymphangiogenesis. In the wounds of 3-5 days after injury, anti-VEGFR-3 immunopositive signals unevenly appeared in 5'-Nase-positive lymphatic vessels in the subcutaneous tissue. A few small circular and irregular lymphatic-like structures with VEGFR-3 expression scattered in the dermal and subcutaneous tissues. Between days 7 and 15 of the wounds, numerous accumulated vasculatures were stained for 5'-Nase and PECAM-1, extending irregularly along the wound edge. Von Willebrand factor was expressed in the endothelial cells of blood vessels and lymphatics in the subcutaneous tissue. Ultrastructural changes of lymphatic vessels developed at different stages, from lymphatic-like structures to newly formed lymphatic vessels with an extremely thin and indented wall. Endothelial cells of the lymphatic vessel were eventually featured by typical intercellular junctions, which deposited with reaction products of VEGFR-3 and 5'-Nase-cerium but lacked VEGF-C expression. The present findings indicate that VEGF-C-induced lymphangiogenesis occurs from the subcutaneous to the dermis along the wound healing edge, especially in the dermal-subcutaneous transitional area, favorable to growth of regenerating lymphatic vessels.
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PMID:Expression of VEGFR-3 and 5'-nase in regenerating lymphatic vessels of the cutaneous wound healing. 1545 95

The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.
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PMID:Organization and developmental aspects of lymphatic vessels. 1862 90

Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. However, it is poorly understood whether EPCs contribute to lymphangiogenesis. Here, we assessed differentiation of a novel population of EPCs towards lymphatic endothelial cells and their lymphatic formation. CD34(+) VEGFR-3(+) EPCs were isolated from mononuclear cells of human cord blood by fluorescence-activated cell sorting. These cells expressed CD133 and displayed the phenotype of the endothelial cells. Cell colonies appeared at 7-10 days after incubation. The cells of the colonies grew rapidly and could be repeatedly subcultured. After induction with VEGF-C for 2 weeks, CD34(+) VEGFR-3(+) EPCs could differentiate into lymphatic endothelial cells expressing specific markers 5'-nucleotidase, LYVE-1 and Prox-1. The cells also expressed hyaluronan receptor CD44. The differentiated cells had properties of proliferation, migration and formation of lymphatic capillary-like structures in three-dimensional collagen gel and Matrigel. VEGF-C enhanced VEGFR-3 mRNA expression. After interfering with VEGFR-3 siRNA, the effects of VEGF-C were diminished. These results demonstrate that there is a population of CD34(+) VEGFR-3(+) EPCs with lymphatic potential in human cord blood. VEGF-C/VEGFR-3 signalling pathway mediates differentiation of CD34(+) VEGFR-3(+) EPCs towards lymphatic endothelial cells and lymphangiogenesis. Cord blood-derived CD34(+) VEGFR-3(+) EPCs may be a reliable source in transplantation therapy for lymphatic regenerative diseases.
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PMID:CD34+ VEGFR-3+ progenitor cells have a potential to differentiate towards lymphatic endothelial cells. 2445 Apr 75