scholarly journals Insufficient Folding of Type IV Collagen and Formation of Abnormal Basement Membrane-like Structure in Embryoid Bodies Derived from Hsp47-Null Embryonic Stem Cells

2004 ◽  
Vol 15 (10) ◽  
pp. 4467-4475 ◽  
Author(s):  
Yasuhiro Matsuoka ◽  
Hiroshi Kubota ◽  
Eijiro Adachi ◽  
Naoko Nagai ◽  
Toshihiro Marutani ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Embryonic Stem ◽  
Basement Membranes ◽  
Embryoid Bodies ◽  
Null Mouse ◽  
Type I ◽  
Type Iv ◽  
Collagen Secretion

Hsp47 is a molecular chaperone that specifically recognizes procollagen in the endoplasmic reticulum. Hsp47-null mouse embryos produce immature type I collagen and form discontinuous basement membranes. We established Hsp47-/- embryonic stem cell lines and examined formation of basement membrane and production of type IV collagen in embryoid bodies, a model for postimplantation egg-cylinder stage embryos. The visceral endodermal cell layers surrounding Hsp47-/- embryoid bodies were often disorganized, a result that suggested abnormal function of the basement membrane under the visceral endoderm. Rate of type IV collagen secretion by Hsp47-/- cells was fourfold lower than that of Hsp47+/+ cells. Furthermore, type IV collagen secreted from Hsp47-/- cells was much more sensitive to protease digestion than was type IV collagen secreted from Hsp47+/+ cells, which suggested insufficient or incorrect triple helix formation in type IV collagen in the absence of Hsp47. These results indicate for the first time that Hsp47 is required for the molecular maturation of type IV collagen and suggest that misfolded type IV collagen causes abnormal morphology of embryoid bodies.

Role of Lateral Interactions in Type IV Collagen Network Mechanics

2013 ◽  
Author(s):  
Lazarina Gyoneva ◽  
Mohammad F. Hadi ◽  
Yoav Segal ◽  
Kevin D. Dorfman ◽  
Victor H. Barocas
Keyword(s):  
Mechanical Properties ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Hereditary Disease ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Type I ◽  
Lateral Interactions ◽  
Type Iv

The basement membrane is a specialized part of the extra-cellular matrix. It is usually characterized as a scaffold for epithelial cells but in some tissues it serves other, mechanical, roles [1]. The mechanical properties of the basement membrane are mainly determined by one of its main constituents — type IV collagen. Unlike the well-known fibrous type I collagen, collagen IV assembles into planar networks (Fig. 1) [2]. The α 1(IV) and α 2(IV) collagen IV chains assemble into the so-called major chain network, present in all basement membranes. The α 3(IV), α 4(IV), α 5(IV) collagen IV chains form the minor chain network which is found only in the adult basement membranes of the kidney glomerular capillaries (GBM), ocular lens (LBM), cochlea, and the testes [3]. The minor chains have a higher number of cysteine residues, allowing them to form a higher number of lateral interactions. In the minor chain network, the greater potential to interact laterally manifests in the formation of super-coils, which are rarely observed in the major chain network [4]. Increasing the number of cross-links in a polymeric material is known to increase material stiffness; therefore, it is believed that the minor chain network confers basement membranes with additional strength and stability [5]. In the hereditary disease Alport syndrome, a mutation causes the absence of the minor chain network. The GBM and LBM of Alport patients appear weakened and unable to meet their mechanical demands, further supporting this theory [6]. The objective of this study was to evaluate the importance of cross-linking in the minor chains for the mechanical properties of type IV collagen networks, specifically in the GBM and LBM where the absence of the minor chains has an observed mechanical effect.

scholarly journals Abnormal Mucosal Extracellular Matrix Deposition Is Associated with Increased TGF-β Receptor-expressing Mesenchymal Cells in a Mouse Model of Colitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1177-1189 ◽  
Author(s):  
Christine V. Whiting ◽  
John F. Tarlton ◽  
Michael Bailey ◽  
Clare L. Morgan ◽  
Paul W. Bland
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Mouse Model ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Mesenchymal Cells ◽  
Type I ◽  
Matrix Deposition ◽  
Type Iv

Transforming growth factor-β (TGF-β) depresses mucosal inflammation and upregulates extracellular matrix (ECM) deposition. We analyzed TGF-β receptors RI and RII as well as ECM components using the CD4+ T-cell-transplanted SCID mouse model of colitis. The principal change in colitis was an increased proportion of TGF-β RII+ mucosal mesenchymal cells, predominantly α-smooth muscle actin (SMA)+ myofibroblasts, co-expressing vimentin and basement membrane proteins, but not type I collagen. TGF-β RII+ SMA− fibroblasts producing type I collagen were also increased, particularly in areas of infiltration and in ulcers. Type IV collagen and laminin were distributed throughout the gut lamina propria in disease but were restricted to the basement membrane in controls. In areas of severe epithelial damage, type IV collagen was lost and increased type I collagen was observed. To examine ECM production by these cells, mucosal mesenchymal cells were isolated. Cultured cells exhibited a similar phenotype and matrix profile to those of in vivo cells. The data suggested that there were at least two populations of mesenchymal cells responsible for ECM synthesis in the mucosa and that ligation of TGF-β receptors on these cells resulted in the disordered and increased ECM production observed in colitic mucosa.

scholarly journals Extracellular matrix of the human thymus: immunofluorescence studies on frozen sections and cultured epithelial cells.

1985 ◽  
Vol 33 (7) ◽  
pp. 655-664 ◽  
Author(s):  
S Berrih ◽  
W Savino ◽  
S Cohen
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Basement Membranes ◽  
Thymic Epithelial Cells ◽  
Perivascular Spaces ◽  
Type I ◽  
Type Iv

The immunohistochemical detection of elements of the human thymic extracellular matrix in situ and in vitro is described. In the normal thymus, the intracapsular and intraseptal fibers were strongly labeled by anti-type I collagen antiserum. Basement membranes bordering the capsule, septae, and perivascular spaces were intensely stained by anti-type IV collagen, anti-fibronectin, and anti-laminin sera. In hyperplastic myasthenia gravis thymuses, the major changes consisted of discontinuities of the basement membrane adjacent to clusters of epithelial (keratin-containing) cells, among which an unusual connective framework (densely labeled by all the antisera) was observed. In vitro, most epithelial cells were strongly labeled by antifibronectin serum and to a lesser extent by the anti-type IV collagen and anti-laminin sera. In addition, fibronectin, laminin, and type IV collagen were detected in the intercellular spaces bordering the epithelial cells in culture. Results show that thymic epithelial cells participate in the synthesis of extracellular matrix elements, which as a result of their localization and influence on epithelial cell growth, should be regarded as constitutive components of the thymic microenvironment.

scholarly journals The Peculiar Pattern of Type IV Collagen Deposition in Epiretinal Membranes

2019 ◽  
Vol 68 (2) ◽  
pp. 149-162 ◽  
Author(s):  
Marì Regoli ◽  
Gian Marco Tosi ◽  
Giovanni Neri ◽  
Annalisa Altera ◽  
Daniela Orazioli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Active Role ◽  
Basement Membranes ◽  
Type I ◽  
Epiretinal Membranes ◽  
Type Iv ◽  
Fibrotic Disorders ◽  
Fibrotic Disorder

Idiopathic epiretinal membranes are sheets of tissue that develop in the vitreoretinal interface. They are formed by cells and extracellular matrix, and they are considered the expression of a fibrotic disorder of the eye. Confocal and immunoelectron microscopy of the extracellular matrix of excised membranes, revealed high contents of type IV collagen. It was distributed within epiretinal membranes in basement membrane-like structures associated with cells and in interstitial deposits. In both cases, type IV collagen was always associated with type I collagen. Col IV was also coupled with Col VI and laminin. At high magnification, type IV collagen immunolabelling was associated with interstitial deposits and showed a reticular appearance due to the intersection of beaded microfilaments. The microfilaments are about 12 nm in diameter with interbead distance of 30–40 nm. Cells of the epiretinal membranes showed intracellular lysosome-like bodies heavily labeled for type IV collagen suggesting an active role in membrane remodeling. Hence, type IV collagen is not necessarily always associated with basement membranes; the molecular interactions that it may develop when not incorporated in basement membranes are still unknown. It is conceivable, however, that they might have implications in the progression of epiretinal membranes and other fibrotic disorders.

scholarly journals Characterization of α1(IV) Collagen Mutations in Caenorhabditis elegans and the Effects of α1 and α2(IV) Mutations on Type IV Collagen Distribution

1997 ◽  
Vol 137 (5) ◽  
pp. 1185-1196 ◽  
Author(s):  
Malini C. Gupta ◽  
Patricia L. Graham ◽  
James M. Kramer
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Basement Membranes ◽  
Null Alleles ◽  
Temperature Sensitive ◽  
Intracellular Accumulation ◽  
Type Iv ◽  
Collagen Secretion ◽  
Glycine Substitution

Type IV collagen is a major component of basement membranes. We have characterized 11 mutations in emb-9, the α1(IV) collagen gene of Caenorhabditis elegans, that result in a spectrum of phenotypes. Five are substitutions of glycines in the Gly-X-Y domain and cause semidominant, temperature-sensitive lethality at the twofold stage of embryogenesis. One is a glycine substitution that causes recessive, non–temperature-sensitive larval lethality. Three putative null alleles, two nonsense mutations and a deletion, all cause recessive, non–temperature-sensitive lethality at the threefold stage of embryogenesis. The less severe null phenotype indicates that glycine substitution containing mutant chains dominantly interfere with the function of other molecules. The emb-9 null mutants do not stain with anti–EMB-9 antisera and show intracellular accumulation of the α2(IV) chain, LET-2, indicating that LET-2 assembly and/or secretion requires EMB-9. Glycine substitutions in either EMB-9 or LET-2 cause intracellular accumulation of both chains. The degree of intracellular accumulation differs depending on the allele and temperature and correlates with the severity of the phenotype. Temperature sensitivity appears to result from reduced assembly/secretion of type IV collagen, not defective function in the basement membrane. Because the dominant interference of glycine substitution mutations is maximal when type IV collagen secretion is totally blocked, this interference appears to occur intracellularly, rather than in the basement membrane. We suggest that the nature of dominant interference caused by mutations in type IV collagen is different than that caused by mutations in fibrillar collagens.

scholarly journals Biosynthesis of sulphated macromolecules by rabbit lens epithelium. II. Relationship to basement membrane formation.

1984 ◽  
Vol 99 (3) ◽  
pp. 861-869 ◽  
Author(s):  
J G Heathcote ◽  
R R Bruns ◽  
R W Orkin
Keyword(s):  
Basement Membrane ◽  
Type I Collagen ◽  
Heparan Sulphate ◽  
Significant Proportion ◽  
Type I ◽  
Heparan Sulphate Proteoglycan ◽  
Membrane Formation ◽  
Sulphate Proteoglycan ◽  
Type Iv ◽  
Rabbit Lens

Rabbit lens epithelial cells display a similar "cobblestone" morphology and produce the same complement of sulphated macromolecules (also see Heathcote, J.G., and R.W. Orkin, 1984, J. Cell Biol., 99:852-860) whether grown on plastic or glass, dried films of gelatin or type IV collagen with laminin, or on gels of type I collagen. There was no evidence of basement membrane formation by these cells when they were grown on plastic, glass, or dried films. In contrast, cultures that had been grown on gels deposited a discrete basement membrane that followed the contours of the basal surfaces of the cells and in addition, they secreted amorphous basement membrane-like material that diffused into the interstices of the gel and associated with the collagen fibrils of the gel. A significant proportion (approximately 70%) of the heparan sulphate proteoglycan fraction that was secreted into the culture medium (fraction MI) when the cells were grown on plastic became associated with the cell-gel layer in the gel cultures. Further, when basement membrane was isolated by detergent extraction, greater than 90% of the 35S-labeled material present was in this heparan sulphate proteoglycan.

scholarly journals Developmental acquisition of basement membrane heterogeneity: type IV collagen in the avian lens capsule.

1983 ◽  
Vol 97 (3) ◽  
pp. 940-943 ◽  
Author(s):  
J M Fitch ◽  
R Mayne ◽  
T F Linsenmayer
Keyword(s):  
Basement Membrane ◽  
Type Iv Collagen ◽  
Lens Capsule ◽  
Basement Membranes ◽  
Developmentally Regulated ◽  
Membrane Heterogeneity ◽  
Domain Specific ◽  
Type Iv ◽  
Anterior Lens Capsule ◽  
Immunohistochemical Analyses

To investigate potential heterogeneity and developmental changes in basement membranes during embryogenesis, we performed immunohistochemical analyses on lens capsules in chicken embryos of different ages using domain-specific monoclonal antibodies against type IV collagen. We found that the capsule of the newly formed lens stained uniformly with antibodies against this component of basement membranes, but with increasing age and differentiation of the lens cells the anterior lens capsule remained brightly fluorescent while staining of the posterior capsule became relatively much less intense. This antero-posterior gradient of anti-type IV collagen antibody reactivity demonstrated that developmentally-regulated changes can occur within a single, continuous basement membrane.

scholarly journals Expression of extracellular matrix components is regulated by substratum.

1990 ◽  
Vol 110 (4) ◽  
pp. 1405-1415 ◽  
Author(s):  
C H Streuli ◽  
M J Bissell
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Type I Collagen ◽  
Basement Membranes ◽  
Type I ◽  
Collagen Gels ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Cells Cultured

Reconstituted basement membranes and extracellular matrices have been demonstrated to affect, positively and dramatically, the production of milk proteins in cultured mammary epithelial cells. Here we show that both the expression and the deposition of extracellular matrix components themselves are regulated by substratum. The steady-state levels of the laminin, type IV collagen, and fibronectin mRNAs in mammary epithelial cells cultured on plastic dishes and on type I collagen gels have been examined, as has the ability of these cells to synthesize, secrete, and deposit laminin and other, extracellular matrix proteins. We demonstrate de novo synthesis of a basement membrane by cells cultured on type I collagen gels which have been floated into the medium. Expression of the mRNA and proteins of basement membranes, however, are quite low in these cultures. In contrast, the levels of laminin, type IV collagen, and fibronectin mRNAs are highest in cells cultured on plastic surfaces, where no basement membrane is deposited. It is suggested that the interaction between epithelial cells and both basement membrane and stromally derived matrices exerts a negative influence on the expression of mRNA for extracellular matrix components. In addition, we show that the capacity for lactational differentiation correlates with conditions that favor the deposition of a continuous basement membrane, and argue that the interaction between specialized epithelial cells and stroma enables them to create their own microenvironment for accurate signal transduction and phenotypic function.

scholarly journals Characterization of muscle epimysium, perimysium and endomysium collagens

1984 ◽  
Vol 219 (3) ◽  
pp. 1017-1026 ◽  
Author(s):  
N Light ◽  
A E Champion
Keyword(s):  
Connective Tissue ◽  
Sodium Dodecyl Sulphate ◽  
Type Iv Collagen ◽  
Sodium Dodecyl ◽  
Basement Membranes ◽  
Type Iii Collagen ◽  
Type I ◽  
Type V Collagen ◽  
Type Iv ◽  
Type V

In the past it has been proven difficult to separate and characterize collagen from muscle because of its relative paucity in this tissue. The present report presents a comprehensive methodology, combining methods previously described by McCollester [(1962) Biochim. Biophys. Acta 57, 427-437] and Laurent, Cockerill, McAnulty & Hastings [(1981) Anal. Biochem. 113, 301-312], in which the three major tracts of muscle connective tissue, the epimysium, perimysium and endomysium, may be prepared and separated from the bulk of muscle protein. Connective tissue thus prepared may be washed with salt and treated with pepsin to liberate soluble native collagen, or can be washed with sodium dodecyl sulphate to produce a very clean insoluble collagenous product. This latter type of preparation may be used for quantification of the ratio of the major genetic forms of collagen or for measurement of reducible cross-link content to give reproducible results. It was shown that both the epimysium and perimysium contain type I collagen as the major component and type III collagen as a minor component; perimysium also contained traces of type V collagen. The endomysium, the sheaths of individual muscle fibres, was shown to contain both type I and type III collagen as major components. Type V collagen was also present in small amounts, and type IV collagen, the collagenous component of basement membranes, was purified from endomysial preparations. This is the first biochemical demonstration of the presence of type IV collagen in muscle endomysium. The preparation was shown to be very similar to other type IV collagens from other basement membranes on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and was indistinguishable from EHS sarcoma collagen and placenta type IV collagen in the electron microscope after rotary shadowing.

scholarly journals Effects of ECM Proteins and Cationic Polymers on the Adhesion and Proliferation of Rat Islet Cells

2008 ◽  
Vol 2 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Guoping Chen ◽  
Naoki Kawazoe ◽  
Tetsuya Tateishi
Keyword(s):  
Cell Culture ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Islet Cells ◽  
Type Ii Collagen ◽  
Type I ◽  
Cationic Polymers ◽  
Type Iv ◽  
Ecm Proteins ◽  
Cationic Polyelectrolytes

The effects of extracellular matrix (ECM) proteins and cationic polymers on the adhesion and proliferation of rat islet cells, RIN-5F cells, were investigated. ECM proteins of laminin, fibronectin, vitronectin, type I collagen, type II collagen, and type IV collagen, and cationic polyelectrolytes of poly(L-lysine) and poly(allylamine) were coated on the wells of polystyrene cell culture plates. Their effects on the adhesion and proliferation of RIN-5F in serum-free and serum mediums were compared. The cell number on the laminin-coated surface was the highest among the coated surfaces. Laminin promoted cell adhesion more strongly than did the other ECM proteins and cationic polyelectrolytes. Vitronectin, type IV collagen, and poly(L-lysine) showed moderate effects, but type I collagen and type II collagen did not have any effects on adhesion and proliferation compared with the uncoated polystyrene cell culture plate. Fibronectin promoted cell adhesion but not cell proliferation. Cationic poly(allylamine) had an inhibitory effect in serum-free medium and for longterm culture in serum medium. The ECM proteins of laminin, vitronectin, and type IV collagen, and cationic poly(Llysine) will be useful for the surface modification and construction of biomaterials and scaffolds for islet cell culture and tissue engineering.

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