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The International Journal of... Mar 1993The mouse embryonal carcinoma lines PCC4-F and F9 have played important roles in the isolation and characterization of the two ubiquitous basement membrane proteins,... (Review)
Review
The mouse embryonal carcinoma lines PCC4-F and F9 have played important roles in the isolation and characterization of the two ubiquitous basement membrane proteins, laminin and entactin. The contributions of these cells to our work on extracellular matrices are briefly summarized. The in vitro differentiation of PCC4-F gives rise to a multiplicity of cell types. Two of these cell types have been propagated as cell lines. One of these, M1536-B3, synthesizes and deposits copious quantities of extracellular matrix glycoproteins, which led to the initial discovery and characterization of laminin and entactin. In addition, M1536-B3 provides a model system for analyzing the assembly of laminin and the laminin-entactin complex and for manipulating extracellular matrix structure and composition. The other cell line, 4CQ, synthesizes a matrix consisting of fibronectin and entactin. F9 cells differentiate to endodermal cells in response to retinoic acid and dibutyryl cyclic AMP (Strickland and Mahdavi, Cell 15: 393-402, 1978). The differentiated cells synthesize basement membrane components and provided the probes for the cDNA cloning of entactin and the three chains of laminin. The F9 cells have been widely employed to examine the regulation of expression of the laminin and entactin genes.
Topics: Animals; Basement Membrane; Laminin; Membrane Glycoproteins; Mice; Neoplasm Proteins; Teratoma
PubMed: 8507559
DOI: No ID Found -
Molecular Neurodegeneration Dec 2021Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key... (Review)
Review
BACKGROUND
Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation.
MAIN BODY
The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed.
CONCLUSIONS
Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.
Topics: Alzheimer Disease; Basement Membrane; Blood-Brain Barrier; Glymphatic System; Humans; Neurodegenerative Diseases
PubMed: 34876200
DOI: 10.1186/s13024-021-00502-y -
The FEBS Journal Dec 2015Basement membranes (BMs) are thin sheets of extracellular matrix that outline epithelia, muscle fibers, blood vessels and peripheral nerves. The current view of BM... (Review)
Review
Basement membranes (BMs) are thin sheets of extracellular matrix that outline epithelia, muscle fibers, blood vessels and peripheral nerves. The current view of BM structure and functions is based mainly on transmission electron microscopy imaging, in vitro protein binding assays, and phenotype analysis of human patients, mutant mice and invertebrata. Recently, MS-based protein analysis, biomechanical testing and cell adhesion assays with in vivo derived BMs have led to new and unexpected insights. Proteomic analysis combined with ultrastructural studies showed that many BMs undergo compositional and structural changes with advancing age. Atomic force microscopy measurements in combination with phenotype analysis have revealed an altered mechanical stiffness that correlates with specific BM pathologies in mutant mice and human patients. Atomic force microscopy-based height measurements strongly suggest that BMs are more than two-fold thicker than previously estimated, providing greater freedom for modelling the large protein polymers within BMs. In addition, data gathered using BMs extracted from mutant mice showed that laminin has a crucial role in BM stability. Finally, recent evidence demonstrate that BMs are bi-functionally organized, leading to the proposition that BM-sidedness contributes to the alternating epithelial and stromal tissue arrangements that are found in all metazoan species. We propose that BMs are ancient structures with tissue-organizing functions and were essential in the evolution of metazoan species.
Topics: Animals; Basement Membrane; Humans; Microscopy, Atomic Force; Proteomics
PubMed: 26299746
DOI: 10.1111/febs.13495 -
Biomolecules Nov 2020One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal... (Review)
Review
One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal junction-a complex network of extracellular matrix macromolecules that connect the outer epidermal layer to the underlying dermis. This junction provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behavior. It displays a distinctive microarchitecture characterized by an undulating pattern, strengthening dermal-epidermal connectivity and crosstalk. The optimal stiffness arising from the overall molecular organization, together with characteristic anchoring complexes, keeps the dermis and epidermis layers extremely well connected and capable of proper epidermal renewal and regeneration. Due to intrinsic and extrinsic factors, a large number of structural and biological changes accompany skin aging. These changes progressively weaken the dermal-epidermal junction substructure and affect its functions, contributing to the gradual decline in overall skin physiology. Most changes involve reduced turnover or altered enzymatic or non-enzymatic post-translational modifications, compromising the mechanical properties of matrix components and cells. This review combines recent and older data on organization of the dermal-epidermal junction, its mechanical properties and role in mechanotransduction, its involvement in regeneration, and its fate during the aging process.
Topics: Basement Membrane; Epidermis; Humans; Keratinocytes; Skin Aging
PubMed: 33260936
DOI: 10.3390/biom10121607 -
Experimental Eye Research Dec 2020The Descemet's membrane (DM) and the lens capsule (LC) are two ocular basement membranes (BMs) that are essential in maintaining stability and structure of the cornea...
The Descemet's membrane (DM) and the lens capsule (LC) are two ocular basement membranes (BMs) that are essential in maintaining stability and structure of the cornea and lens. In this study, we investigated the proteomes and biomechanical properties of these two materials to uncover common and unique properties. We also screened for possible protein changes during diabetes. LC-MS/MS was used to determine the proteomes of both BMs. Biomechanical measurements were conducted by atomic force microscopy (AFM) in force spectroscopy mode, and complemented with immunofluorescence microscopy. Proteome analysis showed that all six existing collagen IV chains represent 70% of all LC-protein, and are thus the dominant components of the LC. The DM on the other hand is predominantly composed of a single protein, TGF-induced protein, which accounted for around 50% of all DM-protein. Four collagen IV-family members in DM accounted for only 10% of the DM protein. Unlike the retinal vascular BMs, the LC and DM do not undergo significant changes in their protein compositions during diabetes. Nanomechanical measurements showed that the endothelial/epithelial sides of both BMs are stiffer than their respective stromal/anterior-chamber sides, and both endothelial and stromal sides of the DM were stiffer than the epithelial and anterior-chamber sides of the LC. Long-term diabetes did not change the stiffness of the DM and LC. In summary, our analyses show that the protein composition and biomechanical properties of the DM and LC are different, i.e., the LC is softer than DM despite a significantly higher concentration of collagen IV family members. This finding is unexpected, as collagen IV members are presumed to be responsible for BM stiffness. Diabetes had no significant effect on the protein composition and the biomechanical properties of both the DM and LC.
Topics: Aged; Basement Membrane; Chromatography, Liquid; Cornea; Descemet Membrane; Elasticity; Eye Proteins; Female; Humans; Lens Capsule, Crystalline; Male; Microscopy, Atomic Force; Middle Aged; Tandem Mass Spectrometry
PubMed: 33147472
DOI: 10.1016/j.exer.2020.108326 -
Journal of Clinical Pathology.... 1978
Review
Topics: Animals; Antibodies; Basement Membrane; Blood Glucose; Collagen; Diabetes Mellitus; Fibrin; Glycoproteins; Humans; Hydroxylysine; Kidney Glomerulus; Permeability
PubMed: 365894
DOI: No ID Found -
Kidney International Jan 1993The pathogenesis of the multiple structural lesions in diabetic nephropathy remains debated, and likely is multifactorial. The uniform thickening of the renal basement... (Review)
Review
The pathogenesis of the multiple structural lesions in diabetic nephropathy remains debated, and likely is multifactorial. The uniform thickening of the renal basement membranes lining the glomerular and tubular elements appears to be a consequence of the metabolic perturbations which are directly related to hyperglycemia. While most investigations have focused on the increased accumulation of extracellular matrix in the glomerular basement membrane and the mesangium, and their relation to derangements in glomerular function, little is known regarding the pathogenesis and the significance of the tubulointerstitial changes and the thickened tubular basement membrane (TBM). It is possible that these latter changes are causally related to the cellular hypertrophy of the renal tubular epithelium that lines the TBM. It has been postulated that in the earlier stages of the disease, hyperglycemia induces renal tubular hypertrophy and stimulates the synthesis of the various matrix components which are normal constituents of the TBM. Later, the structural composition of the TBM is susceptible to further modifications by non-enzymatic glycation, and this aberrant process may impart a relative resistance to matrix degradation leading to a slow turnover. In vitro investigations on murine proximal tubule cells in culture have provided evidence that elevated ambient glucose is a sufficient stimulus for cellular hypertrophy and increased biosynthesis of collagen type IV, the predominant constituent of TBM. High glucose levels increase steady-state collagen IV mRNA, partly due to transcriptional activation of cis-acting elements of the gene which are controlled by putative glucose-responsive trans-acting proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Basement Membrane; Collagen; Diabetes Mellitus; Diabetic Nephropathies; Humans; Kidney Tubules
PubMed: 8433550
DOI: 10.1038/ki.1993.19 -
International Journal of Experimental... Jun 2019This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into... (Review)
Review
This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling-even though cells in 3D can still display prominent focal adhesions. Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, "nuclear piston" migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self-assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis-numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell-matrix interactions.
Topics: Animals; Basement Membrane; Cell Adhesion; Cell Movement; Extracellular Matrix; Humans; Morphogenesis; Signal Transduction
PubMed: 31179622
DOI: 10.1111/iep.12329 -
European Journal of Biochemistry Apr 1989Collagen type IV, laminin, heparan sulfate proteoglycans, nidogen (entactin) and BM-40 (osteonectin, SPARC) represent major structural proteins of basement membranes.... (Review)
Review
Collagen type IV, laminin, heparan sulfate proteoglycans, nidogen (entactin) and BM-40 (osteonectin, SPARC) represent major structural proteins of basement membranes. They are well-characterized in their domain structures, amino acid sequences and potentials for molecular interactions. Such interactions include self-assembly processes and heterotypic binding between individual constituents, as well as binding of calcium (laminin, BM-40) and are likely to be used for basement membrane assembly. Laminin, collagen IV and nidogen also possess several cell-binding sites which interact with distinct cellular receptors. Some evidence exists that those interactions are involved in the control of cell behaviour. These observations have provided a more defined understanding of basement membrane function and the definition of new research goals in the future.
Topics: Animals; Basement Membrane; Humans; Membrane Proteins; Structure-Activity Relationship
PubMed: 2653817
DOI: 10.1111/j.1432-1033.1989.tb14673.x -
Journal of Refractive Surgery... Aug 2019To provide an overview of the importance of the coordinated role of the epithelial basement membrane (EBM) and Descemet's basement membrane (DBM) in modulating scarring... (Review)
Review
PURPOSE
To provide an overview of the importance of the coordinated role of the epithelial basement membrane (EBM) and Descemet's basement membrane (DBM) in modulating scarring (fibrosis) in the cornea after injuries, infections, surgeries, and diseases of the cornea.
METHODS
Literature review.
RESULTS
Despite their molecular and ultrastructural differences, the EBM and DBM act in a coordinated fashion to modulate the entry of transforming growth factor beta (TGF-β) and other growth factors from the epithelium/tear film and aqueous humor, respectively, into the corneal stroma where persistent levels of these modulators trigger the development and persistence of myofibroblasts that produced disordered, opaque extracellular matrix not usually present in the corneal stroma. The development of these myofibroblasts and the extracellular matrix they produce is often detrimental to visual function of the cornea after penetrating keratoplasty, LASIK buttonhole flaps, persistent epithelial defects, microbial keratitis, Descemet stripping automated endothelial keratoplasty, or Descemet membrane endothelial keratoplasty, while being beneficial in other situations such as the scarred edge of LASIK flaps and donor-recipient interface in penetrating keratoplasty. Efforts to modulate the repair or replacement of the EBM and DBM, and thereby the development or disappearance of myofibroblasts, should be a major emphasis of treatments provided by refractive and corneal surgeries, infections, trauma, or diseases of the cornea.
CONCLUSIONS
The EBM and DBM are critical modulators of the localization of profibrotic growth factors, such as TGF-β, that modulate the development and persistence of myofibroblasts that produce corneal scars (stromal fibrosis). Therapeutic efforts to regenerate or repair EBM and/or DBM, and interfere with the development of myofibroblasts or facilitate their disappearance are often the key to clinical outcomes. [J Refract Surg. 2019;35(8):506-516.].
Topics: Basement Membrane; Cornea; Corneal Injuries; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Epithelium, Corneal; Fibrosis; Humans; Keratomileusis, Laser In Situ; Photorefractive Keratectomy
PubMed: 31393989
DOI: 10.3928/1081597X-20190625-02