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Journal of Cerebral Blood Flow and... Oct 2017The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs... (Review)
Review
The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.
Topics: Basement Membrane; Blood-Brain Barrier; Brain; Brain Diseases; Endothelium, Vascular; Humans
PubMed: 28753105
DOI: 10.1177/0271678X17722436 -
Current Pharmaceutical Design 2009Basement membranes are sheet-like cell-adherent extracellular matrices that serve as cell substrata and solid-phase agonists, contributing to tissue organization,... (Review)
Review
Basement membranes are sheet-like cell-adherent extracellular matrices that serve as cell substrata and solid-phase agonists, contributing to tissue organization, stability and differentiation. These matrices are assembled as polymers of laminins and type IV collagens that are tethered to nidogens and proteoglycans. They bind to cell surface molecules that include signal-transducing receptors such as the integrins and dystroglycan and form attachments to adjacent connective tissues. The cell receptors, in turn, provide links between the matrix and underlying cytoskeleton. Genetic diseases of basement membrane and associated components, collectively the basement membrane zone, disrupt the extracellular matrix and/or its linkages to affect nerve, muscle, skin, kidney and other tissues. These diseases can arise due to a loss of matrix integrity, adhesion strength and/or receptor-mediated signaling. An understanding of the mechanisms of basement membrane zone assembly and resulting structure can provide insights into the development of normal tissues and the pathogenic mechanisms that underlie diverse disorders.
Topics: Agrin; Animals; Basement Membrane; Collagen; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Humans; Laminin; Membrane Glycoproteins; Myelin Sheath; Neuromuscular Diseases; Stromal Cells
PubMed: 19355968
DOI: 10.2174/138161209787846766 -
Current Opinion in Genetics &... Dec 2017Cell invasion is a specialized cell behavior that likely co-evolved with the emergence of basement membranes in metazoans as a mechanism to break down the barriers that... (Review)
Review
Cell invasion is a specialized cell behavior that likely co-evolved with the emergence of basement membranes in metazoans as a mechanism to break down the barriers that separate tissues. A variety of conserved and lineage-specific biological processes that occur during development and homeostasis rely on cell invasive behavior. Recent innovations in genome editing and live-cell imaging have shed some light on the programs that mediate acquisition of an invasive phenotype; however, comparative approaches among species are necessary to understand how this cell behavior evolved. Here, we discuss the contexts of cell invasion, highlighting both established and emerging model systems, and underscore gaps in our understanding of the evolution of this key cellular behavior.
Topics: Animals; Basement Membrane; Biological Evolution; Caenorhabditis elegans; Cell Communication; Gene Editing
PubMed: 28881331
DOI: 10.1016/j.gde.2017.08.003 -
Cell Adhesion & Migration 2014Basement membranes are thin sheets of self-assembled extracellular matrices that are essential for embryonic development and for the homeostasis of adult tissues. They... (Review)
Review
Basement membranes are thin sheets of self-assembled extracellular matrices that are essential for embryonic development and for the homeostasis of adult tissues. They play a role in structuring, protecting, polarizing, and compartmentalizing cells, as well as in supplying them with growth factors. All basement membranes are built from laminin and collagen IV networks stabilized by nidogen/perlecan bridges. The precise composition of basement membranes, however, varies between different tissues. Even though basement membranes represent physical barriers that delimit different tissues, they are breached in many physiological or pathological processes, including development, the immune response, and tumor invasion. Here, we provide a brief overview of the molecular composition of basement membranes and the process of their assembly. We will then illustrate the heterogeneity of basement membranes using two examples, the epithelial basement membrane in the gut and the vascular basement membrane. Finally, we examine the different strategies cells use to breach the basement membrane.
Topics: Animals; Basement Membrane; Cell Movement; Humans; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 24727304
DOI: 10.4161/cam.28733 -
Journal of Anatomy Jul 1998Laminins are a family of multifunctional macromolecules, ubiquitous in basement membranes, and represent the most abundant structural noncollagenous glycoproteins of... (Review)
Review
Laminins are a family of multifunctional macromolecules, ubiquitous in basement membranes, and represent the most abundant structural noncollagenous glycoproteins of these highly specialised extracellular matrices. Their discovery started with the difficult task of isolating molecules produced by cultivated cells or extracted from tissues. The development of molecular biology techniques has facilitated and accelerated the identification and the characterisation of new laminin variants making it feasible to identify full-length polypeptides which have not been purified. Further, genetically engineered laminin fragments can be generated for studies of their structure-function relationship, permitting the demonstration that laminins are involved in multiple interactions with themselves, with other components of the basal lamina, and with cells. It endows laminins with a central role in the formation, the architecture, and the stability of basement membranes. In addition, laminins may both separate and connect different tissues, i.e. the parenchymal and the interstitial connective tissues. Laminins also provide adjacent cells with a mechanical scaffold and biological information either directly by interacting with cell surface components, or indirectly by trapping growth factors. In doing so they trigger and control cellular functions. Recently, the structural and biological diversity of the laminins has started to be elucidated by gene targeting and by the identification of laminin defects in acquired or inherited human diseases. The consequent phenotypes highlight the pivotal role of laminins in determining heterogeneity in basement membrane functions.
Topics: Animals; Basement Membrane; Epidermolysis Bullosa; Extracellular Matrix; Gene Targeting; Humans; Integrins; Isomerism; Laminin; Mice; Mice, Mutant Strains; Muscular Dystrophies
PubMed: 9758133
DOI: 10.1046/j.1469-7580.1998.19310001.x -
Investigative Ophthalmology & Visual... Sep 2013The corneal epithelial basement membrane (BM) is positioned between basal epithelial cells and the stroma. This highly specialized extracellular matrix functions not... (Review)
Review
The corneal epithelial basement membrane (BM) is positioned between basal epithelial cells and the stroma. This highly specialized extracellular matrix functions not only to anchor epithelial cells to the stroma and provide scaffolding during embryonic development but also during migration, differentiation, and maintenance of the differentiated epithelial phenotype. Basement membranes are composed of a diverse assemblage of extracellular molecules, some of which are likely specific to the tissue where they function; but in general they are composed of four primary components--collagens, laminins, heparan sulfate proteoglycans, and nidogens--in addition to other components such as thrombospondin-1, matrilin-2, and matrilin-4 and even fibronectin in some BM. Many studies have focused on characterizing BM due to their potential roles in normal tissue function and disease, and these structures have been well characterized in many tissues. Comparatively few studies, however, have focused on the function of the epithelial BM in corneal physiology. Since the normal corneal stroma is avascular and has relatively low keratocyte density, it is expected that the corneal BM would be different from the BM in other tissues. One function that appears critical in homeostasis and wound healing is the barrier function to penetration of cytokines from the epithelium to stroma (such as transforming growth factor β-1), and possibly from stroma to epithelium (such as keratinocyte growth factor). The corneal epithelial BM is also involved in many inherited and acquired corneal diseases. This review examines this structure in detail and discusses the importance of corneal epithelial BM in homeostasis, wound healing, and disease.
Topics: Animals; Basement Membrane; Corneal Diseases; Epithelium, Corneal; Humans
PubMed: 24078382
DOI: 10.1167/iovs.13-12547 -
Developmental Biology Oct 2001An experimental paradigm was devised to remove the retinal basal lamina for defined periods of development: the basal lamina was dissolved by injecting collagenase into...
An experimental paradigm was devised to remove the retinal basal lamina for defined periods of development: the basal lamina was dissolved by injecting collagenase into the vitreous of embryonic chick eyes, and its regeneration was induced by a chase with mouse laminin-1 and alpha2-macroglobulin. The laminin-1 was essential in reconstituting a new basal lamina and could not be replaced by laminin-2 or collagen IV, whereas the macroglobulin served as a collagenase inhibitor that did not directly contribute to basal lamina regeneration. The regeneration occurred within 6 h after the laminin-1 chase by forming a morphologically complete basal lamina that included all known basal lamina proteins from chick embryos, such as laminin-1, nidogen-1, collagens IV and XVIII, perlecan, and agrin. The temporary absence of the basal lamina had dramatic effects on retinal histogenesis, such as an irreversible retraction of the endfeet of the neuroepithelial cells from the vitreal surface of the retina, the formation of a disorganized ganglion cell layer with an increase in ganglion cells by 30%, and the appearance of multiple retinal ectopias. Finally, basal lamina regeneration was associated with aberrant axons failing to correctly enter the optic nerve. The present data demonstrate that a transient disruption of the basal lamina leads to dramatic and probably irreversible aberrations in the histogenesis in the developing central nervous system.
Topics: Agrin; Animals; Antibodies, Monoclonal; Axons; Basement Membrane; Central Nervous System; Chick Embryo; Collagen; Collagenases; DNA, Complementary; Enzyme Inhibitors; Epithelial Cells; Heparan Sulfate Proteoglycans; Immunohistochemistry; In Situ Hybridization; Laminin; Matrix Metalloproteinase Inhibitors; Mice; Microscopy, Fluorescence; Neurons; Phenotype; Regeneration; Retina; Time Factors; alpha-Macroglobulins
PubMed: 11783995
DOI: 10.1006/dbio.2001.0396 -
The Journal of Cell Biology Aug 1985Primary cultures that contain only Schwann cells and sensory nerve cells synthesize basal lamina. The assembly of this basal lamina appears to be essential for normal...
Primary cultures that contain only Schwann cells and sensory nerve cells synthesize basal lamina. The assembly of this basal lamina appears to be essential for normal Schwann cell development. In this study, we demonstrate that Schwann cells synthesize two major heparan sulfate-containing proteoglycans. Both proteoglycans band in dissociative CsCl gradients at densities less than 1.4 g/ml, and therefore, presumably, have relatively low carbohydrate-to-protein ratios. The larger of these proteoglycans elutes from Sepharose CL-4B in 4 M guanidine hydrochloride (GuHCl) at a Kav of 0.21 and contains heparan sulfate and chondroitin sulfate chains of Mr 21,000 in a ratio of approximately 3:1. This proteoglycan is extracted from cultures by 4 M GuHCl but not Triton X-100 and accumulates only when Schwann cells are actively synthesizing basal lamina. The smaller proteoglycan elutes from Sepharose CL-4B at a Kav of 0.44 and contains heparan sulfate and chondroitin sulfate chains of Mr 18,000 in a ratio of approximately 4:1. This proteoglycan is extracted by 4 M GuHCl or by Triton X-100. The accumulation of this proteoglycan is independent of basal lamina production.
Topics: Animals; Antibodies, Monoclonal; Basement Membrane; Cell Division; Cell Membrane; Cells, Cultured; Chondroitin Sulfate Proteoglycans; Glycosaminoglycans; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Macromolecular Substances; Mice; Neurons; Octoxynol; Polyethylene Glycols; Proteoglycans; Rats; Rats, Inbred Strains; Schwann Cells
PubMed: 3160714
DOI: 10.1083/jcb.101.2.660 -
Nature Jun 2020Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction. However, recent...
Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction. However, recent work has revealed roles for basement membrane remodelling in global tissue morphogenesis. Upon implantation, the epiblast and extraembryonic ectoderm of the mouse embryo become enveloped by a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis. However, the mechanical role of the basement membrane in post-implantation embryogenesis remains unknown. Here we demonstrate the importance of spatiotemporally regulated basement membrane remodelling during early embryonic development. Specifically, we show that Nodal signalling directs the generation and dynamic distribution of perforations in the basement membrane by regulating the expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior-posterior axis further regulates basement membrane remodelling by localizing Nodal signalling-and therefore the activity of matrix metalloproteinases and basement membrane perforations-to the posterior side of the embryo. Perforations on the posterior side are essential for primitive-streak extension during gastrulation by rendering the basement membrane of the prospective primitive streak more prone to breaching. Thus spatiotemporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.
Topics: Animals; Basement Membrane; Blastocyst; Embryo, Mammalian; Embryonic Development; Extracellular Matrix; Female; Gastrula; Male; Matrix Metalloproteinases; Mice; Nodal Signaling Ligands; Primitive Streak
PubMed: 32523119
DOI: 10.1038/s41586-020-2264-2 -
Annals of the Rheumatic Diseases Feb 2006To study the expression of laminin and type IV collagen as biomarkers of the organisation of the basal lamina of acini and ducts in labial salivary glands from patients... (Comparative Study)
Comparative Study
OBJECTIVE
To study the expression of laminin and type IV collagen as biomarkers of the organisation of the basal lamina of acini and ducts in labial salivary glands from patients with Sjögren's syndrome, and to relate this organisation to inflammatory cell invasion of acini and ducts.
METHODS
Immunohistochemistry for laminin and type IV collagen was undertaken on sections of labial salivary glands from 30 patients with Sjögren's syndrome, 10 control subjects, and 24 controls with chronic sialoadenitis. Immunohistochemistry reaction, alterations to cell morphology, and the presence of inflammatory cells in acini and ducts were evaluated and scored using a semiquantitative method.
RESULTS
Changes in the expression of laminin and type IV collagen in the basal lamina of acini and ducts of labial salivary glands from patients with Sjögren's syndrome were more pronounced than in labial salivary glands from control groups. A remarkable characteristic was the disorganisation of the basal lamina in the labial salivary glands in Sjögren's syndrome. The pattern of immunoreactivity of the basal lamina of other structures (for example, blood vessels) did not change. In Sjögren's syndrome, invasion of cytotoxic T lymphocytes was only observed in acini and ducts which had a disorganised basal lamina.
CONCLUSIONS
The high state of disorganisation of the basal lamina of acini and ducts could allow invasion of cytotoxic T lymphocytes in Sjögren's syndrome, contributing to cell death and ductal hyperplasia.
Topics: Adult; Basement Membrane; Biomarkers; Case-Control Studies; Chronic Disease; Collagen Type IV; Female; Humans; Immunohistochemistry; Laminin; Lip; Male; Middle Aged; Salivary Ducts; Salivary Glands, Minor; Sialadenitis; Sjogren's Syndrome; T-Lymphocytes, Cytotoxic
PubMed: 16014676
DOI: 10.1136/ard.2004.033837