Showing papers on "Extracellular matrix component published in 1995"

Advanced protein glycosylation in diabetes and aging

Abstract: Products of advanced protein glycosylation (advanced glycation end products, or AGEs) accumulate in tissues as a function of time and sugar concentration. AGEs induce permanent abnormalities in extracellular matrix component function, stimulate cytokine and reactive oxygen species production through AGE-specific receptors, and modify intracellular proteins. Pharmacologic inhibition of AGE formation in long-term diabetic animals prevents diabetic retinopathy, nephropathy, neuropathy, and arterial abnormalities in animal models. Clinical trials in humans are currently in progress.

Pericellular mobilization of the tissue-destructive cysteine proteinases, cathepsins B, L, and S, by human monocyte-derived macrophages.

Abstract: Human macrophages are believed to damage host tissues in chronic inflammatory disease states, but these cells have been reported to express only modest degradative activity in vitro. However, while examining the ability of human monocytes to degrade the extracellular matrix component elastin, we identified culture conditions under which the cells matured into a macrophage population that displayed a degradative phenotype hundreds of times more destructive than that previously ascribed to any other cell population. The monocyte-derived macrophages synthesized elastinolytic matrix metalloproteinases (i.e., gelatinase B and matrilysin) as well as cysteine proteinases (i.e., cathepsins B, L, and S), but only the cathepsins were detected in the extracellular milieu as fully processed, mature enzymes by either vital fluorescence or active-site labeling. Consistent with these observations, macrophage-mediated elastinolytic activity was not affected by matrix metalloproteinase inhibitors but could be almost completely abrogated by inhibiting cathepsins L and S. These data demonstrate that human macrophages mobilize cysteine proteinases to arm themselves with a powerful effector mechanism that can participate in the pathophysiologic remodeling of the extracellular matrix.

Molecular basis of interactions between regenerating adult rat thalamic axons and Schwann cells in peripheral nerve grafts. II. Tenascin-C.

Abstract: Tenascin-C is a developmentally regulated extracellular matrix component There is evidence that it may be involved in axon growth and regeneration in peripheral nerves We have used in situ hybridization and immunocytochemistry to investigate the association of tenascin-C with central nervous system axons regenerating through a peripheral nerve autograft inserted into the thalamus of adult rats Between 3 days and 4 weeks after implantation, tenascin-C immunoreactivity was increased in the grafts, first at the graft/brain interface, then in the endoneurium of the graft, and finally within the Schwann cell columns of the graft By electron microscopy, reaction product was present around collagen fibrils and basal laminae in the endoneurium, but the heaviest deposits were found at the surface of regenerating thalamic axons within Schwann cell columns Schwann cell surfaces were not associated with tenascin-C reaction product except where they faced the tenascin-rich basal lamina or were immediately opposite axons surrounded by tenascin-C By 8 weeks after graft implantation tenascin-C in the endoneurium and around axons of the graft was decreased In the brain parenchyma around the proximal part of the graft, axonal sprouts associated with tenascin-C could not be identified earlier than 2 weeks after grafting and were sparse at this stage Larger numbers of such axons were present at 8-13 weeks after grafting and were located predominantly where the glia limitans between brain and graft appeared to be incomplete, suggesting that the tenascin-C may have penetrated the brain parenchyma from the graft By in situ hybridization, cells expressing tenascin-C mRNA (probably Schwann cells) appeared first at the brain/graft interface 3 days after grafting and thereafter were mainly located within the grafts Lightly labelled cells containing tenascin-C mRNA (probably glial cells) were scattered in the thalamic parenchyma both ipsilateral and contralateral to the graft and a few heavily labelled cells were located very close to the tip of the graft These results show that regenerating adult thalamic axons, unlike regenerating peripheral axons, become intimately associated with peripheral nerve graft-derived tenascin-C, suggesting that they express a tenascin-C receptor, as many neurons do during development, and that tenascin-C derived from Schwann cells may play a role in the regenerative growth of such axons through the grafts (C) 1995 Wiley-Liss, Inc

Control of cell growth in a bioartificial organ with extracellular matrix coated microcarriers

Abstract: Methods and compositions are provided for controlling cell distribution within an implantable bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory. Cells can be grown on microcarriers and then loaded into the bioartificial organ. The microcarriers may be coated with an extracellular matrix component such as collagen to cause decreased cell proliferation or increased cell differentiation. Microcarriers containing cells can be suspended in a proliferation inhibiting hydrogel matrix prior to encapsulation.

Material to be worn on the eyeball

Abstract: The present invention provides semi-spherical materials to be worn on the eyeball, such as contact lenses for visual acuity correction or medical treatment use, cornea protecting materials, controlled drug release contact lenses and the like, which comprise, as a main component, a glycosaminoglycan existing in the living body as an extracellular matrix component of connective tissues and satisfy various requirements such as a dimensional stability, transparency, surface water wettability, tissue compatibility, oxygen permeability and the like. In other words, the material to be worn on the eyeball has a shape of semi-spherical surface compatible in shape with the mammalian eyeball and has biological and surface-physical compatibilities with ophthalmic tissues and comprises, as a main component, a substantially transparent photocured crosslinked-glycosaminoglycan obtained by allowing photoreactive groups covalently bonded to a glycosaminoglycan to crosslink mutually by photoirradiation.

Localization of amyloid P component in human brain: Vascular staining patterns and association with alzheimer's disease lesions

Abstract: Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristic histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular β-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium. © 1995 Wiley-Liss, Inc.

Altered Extracellular Matrix Component Gene Expression in Murine Polycystic Kidney

Abstract: The DBA/2FG-pcy mouse has a form of slowly progressive kidney disease that appears similar in many respects to that seen in the autosomal dominant form of human polycystic kidney disease. This study was designed to assess how the expression of extracellular matrix component genes is regulated in a model of murine polycystic kidney disease and control DBA/2 mice at 8, 16, and 30 weeks of age. The mRNA levels encoding for collagen IV, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, fibronectin, and collagens I and III increased with the progression of cystic lesions in the kidney of DBA/2FG-pcy mice. At 30 weeks of age, mRNA levels for collagen IV, laminin B1 and B2, heparan sulfate proteoglycan, fibronectin, and collagens I and III were increased 8.1-fold, 7.0-fold, 7.0-fold, 9.8-fold, 7.0-fold, 5.5-fold, and 5.4-fold, respectively, compared to those of control DBA/2 mice. An immunofluorescence study revealed the irregular staining for collagen IV, laminin, heparan sulfate proteoglycan, and collagens I and III around the cysts. These data suggest that changes in the expression of basement membrane components and interstitial collagens are associated with the development of polycystic kidney disease.

A molecular approach to the pathophysiology of the X chromosome-linked Kallmann's syndrome.

Abstract: Summary The human KAL gene is responsible for the X chromosome-linked Kallmann's syndrome, which consists of an association between hypogonadotropic hypogonadism and anosmia (or hyposmia). Additional symptoms are occasionally observed. The olfactory defect is associated with hypoplasia of the olfactory bulbs and tracts. The hypogonadism may be due to a defect in the embryonic migratory process of GnRH-synthesizing neurones from the olfactory pits up to the brain. The human and chicken KAL genes have been isolated. From the amino acid sequences deduced, it has been postulated that the KAL protein is an extracellular matrix component, with putative antiprotease activity and adhesion function. Various point mutations and, in a few cases, deletions of KAL have been detected in patients. By in situ hybridization, KAL expression has been studied during embryonic development in the chick. From embryonic day 2 (ED2) to ED8, the KAL gene is expressed in various endodermal, mesodermal and ectodermal derivatives, whereas the expression from ED8 is almost entirely restricted to definite neuronal populations in the central nervous system, most of which still express the gene after hatching. According to such a spatiotemporal pattern of expression, we suggest that the KAL gene is involved both in morphogenetic events and in late neuronal differentiation and/or neuronal trophicity. With respect to the olfactory system, the KAL gene is expressed in the mitral cells of the olfactory bulbs from ED8 onwards. In contrast, no expression of the KAL gene is detected at any stage in either the embryonic olfactory epithelium or the surrounding nasal mesenchyme. Therefore, assuming that similar conditions are found in the human embryo, we suggest that the olfactory anomaly in Xlinked Kallmann's syndrome results from a central target cell defect. Current hypotheses regarding the pathophysiology of the GnRH deficiency are also discussed. In situ hybridization experiments in the human embryo, as well as characterization of the KAL protein, are in progress.

Modulation of the expression of interstitial and type-IV collagenases in coculture of HT1080 fibrosarcoma cells and fibroblasts.

Abstract: Members of the metalloproteinase family (MMPs) are known to play a crucial role in the metastatic cascade. Here, we report some investigations about the synthesis of interstitial and type-IV collagenases (gelatinases A and B) in a model of coculture of human fibroblasts and HT 1080 fibrosarcoma cells. The interstitial collagenase activity, mainly found in the conditioned medium of fibroblasts, and its mRNA level were increased in the in vitro coculture model. In contrast, gelatinase A was produced by both cell types. The HT 1080 cells additionally synthesised gelatinase B. In coculture, an enhancement of gelatinase A and the presence of its activated form were observed. Northern blot analysis demonstrated that this enzymatic enhancement occurred at a pretranslational level. The stimulation of the interstitial collagenase activity was partially mediated through soluble factor(s), whereas increased gelatinase A appeared to require direct cell-cell interactions. The extracellular matrix component, type-I collagen, stimulated the enzymatic activities released by the individual cells, but it did not modulate the synthesis of interstitial collagenase in coculture. Our results demonstrate that distinct MMPs are modulated by distinct mechanisms, all depending on specific interactions between tumour cells and host fibroblasts.

Lipids in Predentine and Dentine

Abstract: Using two histochemical methods, malachite green-aldehyde and iodoplatinate, phospholipids were visualized in the predentine of rat incisors in the spaces located between collagen fibers and in dentine as needle-like structures located along individual or groups of mineralizing collagen fibers. The same staining pattern was seen with phospholipase A2-gold. Autoradiographic investigation using 3H choline as labelled precursor, visualized the incorporation of membrane-associated and extracellular choline-containing phosphatidyl choline and sphingomyelin. The cell and membrane-associated labelling decreased gradually between 24 and 4 days, whereas incorporation of the labelled precursor as stable extracellular matrix component was seen in dentine. In addition to these investigations, pharmacologically induced (xuramine) and genetically (Krabbe's disease) lysosomal storage pathology was investigated. Defects due to lipid metabolism alterations were seen in predentine and/or in dentine. The major differences v...

Extracellular matrix component-containing hydrogel thin film

Abstract: PURPOSE: To obtain an extracellular matrix component-containing hydrogel thin film having mechanical strength enough to be useful as a cell culture substrate etc., easy to prepare and excellent in convenience, by hydrating a vitrified matrix gel thin film obtained from an extracellular matrix component. CONSTITUTION: A solution of an extracellular matrix component (e.g. collagen) gelates, and is dried and vitrified. The product is then hydrated into the objective hydrogel thin film. According as necessary, this thin film is integrated with a substrate. The vitrification is carried out by, for example, air-drying of an extracellular matrix component-contg. gel 0.05-5wt.% or so in the final concentration. COPYRIGHT: (C)1996,JPO

Adhesion to Fibronectin Augments Eosinophil Radical Oxygen Products

Abstract: Fibronectin, an extracellular matrix component, is a ligand for very late activation antigen (VLA)-4, which is one of the β1-integrin family of molecules expressed by eosinophils. This study examined the effect of adherence to fibronectin on radical oxygen products from eosinophils. Adhesion of eosinophils to fibronectin resulted in enhancement of eosinophil production of radical oxygen species, as determined by luminol-dependent chemiluminescence of eosinophils stimulated with calcium ionophore. It was concluded that eosinophil adhesion to extracellular matrix via adhesion molecules may be important in the pafhogenesis of allergic inflammation through eosinophil activation.

Cryo-immunogold ultrastructural localization of laminin in adult rat peripheral nerve.

Abstract: Elucidation of the functional roles of the extracellular matrix component laminin in adult peripheral nerve has been hindered by differing accounts of its ultrastructural localization. This is the first report applying the advantages of the cryo-immunogold technique to laminin localization in peripheral nerve. Laminin labelling was found over the basal lamina and possibly over the immediately subjacent Schwann cell plasma membrane, but specific labelling appeared to be absent from other membranes (including those of non-myelinated axon/Schwann cell clusters) and from endoneurial collagen fibrils. It would appear that the functional roles played by laminin in normal adult peripheral nerve are likely to be mediated via its localization in the basal lamina, rather than through a more widespread distribution within the endoneurium.