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Query: UNIPROT:P06889 (Mol)
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Collagens XII and XIV are members of a subfamily of fibril-associated collagens with interrupted triple-helices (FACITs) that facilitate the interactions of adjacent collagen fibrils. Using immunohistochemistry and in situ hybridization, we analyzed the spatial and temporal expression pattern of collagens XII and XIV during bleomycin-induced pulmonary fibrosis. C57Bl mice were treated with bleomycin (1 U, i.p., every other day for 8 days) or saline (control), and lung tissue samples were analyzed 2-12 weeks later. Collagen I protein expression was increased in the lung 2 weeks post bleomycin treatment and persisted for at least 12 weeks. In contrast, collagen XII and XIV expression was low until 4 weeks after bleomycin treatment. Whereas collagen XII expression was greatest between 4 weeks and 8 weeks, expression of collagen XIV persisted from 4 to 12 weeks, which suggests that these two proteins may play distinct roles in the fibrotic process. The mRNA for lysyl oxidase (LOX), an enzyme for cross-linking of collagens, had a delayed increase in the lung after bleomycin administration. It reached a maximum after 8 weeks, and persisted throughout the 12 weeks of the study. These data support the hypothesis that fibrosis is a multistep process that involves both collagen accumulation and changes in the molecules that modulate the biomechanical properties of fibrils.
Anat Rec A Discov Mol Cell Evol Biol 2003 Dec
PMID:Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice. 1461 7

The role played by specific extracellular matrix molecules in normal endocardial cushion differentiation into valves and septa remains to be established. In this respect, type collagen VI is of particular interest because genes encoding the alpha1 and alpha2 chains are located on chromosome 21, and defects involving the atrioventricular (AV) cushions are frequent in trisomy 21. Collagen VI expression was studied in normal human embryonic and fetal hearts (5-18 weeks of development) and compared by immunohistochemistry with results from fetuses (10-16 weeks of development) with trisomy 21. During normal endocardial cushion differentiation (5-8 weeks) there was marked collagen VI expression in the AV cushions, whereas only minor expression was seen in the outflow tract cushions. In the normal fetuses (10-18 weeks), collagen VI in the AV cushions had condensed into a marked zone on the atrial side of the leaflets, as well as subendocardially in other regions of high shear stress. Morphological defects involving the endocardial cushion-derived structures were present in all trisomy 21 cases. An abnormally large membranous septum was observed in three cases. An AV septal defect (AVSD) was present in two, while one had a ventricular septal defect (VSD). Two cases presented with a secondary atrial septal defect (ASDII), and one had an AVSD. Mild to moderate valve dysmorphia was found in all cases. Collagen VI staining in trisomy 21 was more intense than in the normal subjects; however, there were no differences in the spatial expression patterns. We conclude that collagen VI is expressed in the AV cushions and persists during valve differentiation. Collagen VI is more prominent in fetal trisomy 21 hearts than in normal hearts. We hypothesise that collagen VI has a role in the development of heart defects involving endocardial cushion differentiation-specifically in the AV canal, the most common site of malformations affecting children with trisomy 21.
Anat Rec A Discov Mol Cell Evol Biol 2003 Dec
PMID:Collagen type VI expression during cardiac development and in human fetuses with trisomy 21. 1461 10

Human articular chondrocytes (HACs) were isolated from cartilage samples of normal joints and cultivated in monolayer for 56 days. Collagen type I, II, IX, aggrecan, and versican expression was quantified by real-time polymerase chain reaction (PCR). The expression of the genes was highly time-dependent and changed over the culture time. Collagen type I was not present at the beginning of the culture and increased 100-fold during the culture time. Collagen type II and IX expression was found during the entire culture period and decreased more than 100-fold. Aggrecan expression was downregulated 100-fold whereas versican expression increased 10 times. Indices of cell differentiation, defined as ratios of collagen type II to I (CII/I), collagen type IX to I (CIX/I), and aggrecan to versican (Agg/Ver), were significantly higher at the beginning of the culture and decreased over the culture period. The CII/I and CIX/I ratios formed three phases, with a plateau at the beginning, followed by a transition phase and a steady state at the end of the culture time, whereas the Agg/Ver ratio declined constantly. The accurate quantitative assessment of extracellular matrix gene expression in samples of chondrocytes taken from monolayer culture can be used to monitor chondrocyte metabolism as well as changes in the cell differentiation status.
Int J Mol Med 2004 Feb
PMID:Quantitative analysis of gene expression in human articular chondrocytes in monolayer culture. 1471 35

Abnormal gall bladder motor function with delayed emptying and stasis are the contributory factors of gall stone formation. Since collagen is the major contractile protein, this study was designed to find out whether the biochemical and physicochemical changes of collagen contribute to the pathogenesis of gall stone formation. Collagen was isolated from the gall bladder of 25 gall stone patients undergoing cholecystectomy and from that of 20 gall stone free subjects. The levels of total, soluble and insoluble collagen were determined. The activity levels of collagenase (3.4.23.3) and protease (3.4.24.11) were assessed. Levels of susceptibility of collagen to denaturing agents 2 M potassium thiocyanate and 8 M urea were estimated. Aldehyde content, shrinkage temperature and tensile strength were also determined in isolated collagen. SDS-PAGE was carried out and alpha, beta fractions were quantified. The total and insoluble collagen contents were significantly high in gall stone patients. The activity levels of collagenase and protease were significantly low. Elevated levels of lipid peroxides, aldehyde content, shrinkage temperature and tensile strength were observed in gall stone patients. There is a significant elevation in the beta fraction and a decrease in alpha/beta ratio. Ultramicroscopic structure of gall bladder revealed derangement of collagen fibres and altered tissue architecture. The results showed that the qualitative and quantitative alterations in collagen also contribute for the defective contractility and stasis of gall bladder in gall stone patients.
J Biochem Mol Biol Biophys 2002 Dec
PMID:Biochemical and physicochemical changes in collagen isolated from the gall bladder of gall stone patients. 1497 98

The three-dimensional architecture of collagen fibrils in the connective tissue framework and the distribution of collagen types in the goat hypophysis were studied by the cell maceration method in combination with scanning electron microscopy (SEM) and immunohistochemistry. The pars distalis of the adenohypophysis consisted of many cell clusters. SEM revealed that the wall of cell clusters appeared as various-sized flat bundles of collagen fibrils woven in a basket-like configuration. In the pars tuberalis, the aggregates of collagen fibrils were denser and bundles thicker compared to the pars distalis. The density of collagen fibrils changed from the pars tuberalis to pars distalis without a distinct border. The collagen framework in the pars intermedia was mainly divided into three parts, the dorsal region with large hollows, the middle region, and the ventral sheet facing the cavum hypophysis. In the lobus nervosus of the neurohypophysis, the collagen network exhibited a sponge-like appearance at low magnification. Collagen fibrils of various sizes consisted of loose wavy bundles distributed around the cavities. Immunohistochemistry revealed types I, III, IV, V, and VI collagen throughout the hypophysis. It is concluded that to maintain structural and functional integration, the components of collagen are in different configurations throughout the regions of the goat hypophysis.
Anat Rec A Discov Mol Cell Evol Biol 2004 Apr
PMID:Three-dimensional architecture and distribution of collagen components in the goat hypophysis. 1505 55

Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that is widely used to address questions of disease pathogenesis and to validate therapeutic targets. Arthritis is normally induced in mice or rats by immunization with autologous or heterologous type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The chief pathological features of CIA include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone, and fibrosis. As in RA, pro-inflammatory cytokines, such as tumor necrosis factor alpha(TNFalpha) and interleukin (IL)-1beta, are abundantly expressed in the arthritic joints of mice with CIA, and blockade of these molecules results in a reduction of disease severity.
Methods Mol Med 2004
PMID:Collagen-induced arthritis as a model for rheumatoid arthritis. 1506 42

Introduction of Salmonella enterica serotype Typhimurium into food products results from its ability to persist in the intestine of healthy livestock by mechanisms that are poorly understood. The non-fimbrial adhesin ShdA is a fibronectin binding protein required for persistent intestinal carriage of S. Typhimurium. We further investigated the molecular mechanism of ShdA-mediated intestinal persistence by determining the binding-site of this receptor in fibronectin. Analysis of ShdA binding to fibronectin proteolytic fragments and to recombinant fibronectin fusion proteins identified the (13)FnIII repeat module of the Hep-2 domain as the primary binding site for this adhesin. The (13)FnIII repeat module of fibronectin contains a cationic cradle formed by six basic residues (R6, R7, R9, R23, K25 and R54) that is a high affinity heparin-binding site conserved among fibronectin sequences from frogs to man. Binding of ShdA to the (13)FnIII repeat module of fibronectin and to a second extracellular matrix protein, Collagen I, could be inhibited by heparin. Furthermore, binding of ShdA to the Hep-2 domain was sensitive to the ionic buffer strength, suggesting that binding involved ionic interactions. We therefore determined whether amino acid substitutions of basic residues in the cationic cradle of the Hep-2 domain that inhibit heparin binding also abrogate binding of ShdA. Combined substitution of R6S and R7S strongly reduced ShdA binding to (13)FnIII. These data suggest that ShdA binds the Hep-2 domain of fibronectin by a mechanism that may mimic binding of the host polysaccharide heparin.
Mol Microbiol 2004 Apr
PMID:The ShdA adhesin binds to the cationic cradle of the fibronectin 13FnIII repeat module: evidence for molecular mimicry of heparin binding. 1506 25

Collagen XVI is a minor component of at least two different extracellular fibrillar networks of specialized regions of skin and cartilage. In skin, collagen XVI is integrated into particular fibrillin-rich microfibrils lacking an amorphous elastin core. In cartilage, collagen XVI is a component of small heterotypic D-banded fibrils, mainly occurring in the territorial matrix of chondrocytes. Here, we present the first direct evidence for the molecular structure and functional properties of these fibril-associated collagens with interrupted triple helices (FACIT). We have expressed recombinantly the full-length alpha1 chain of human collagen XVI in HEK 293 EBNA cells in large quantities using an episomal expression system. Secreted full-length recombinant collagen XVI forms stable disulfide-bonded homotrimers and is rapidly proteolytically processed to distinct fragments at specific protease sequence motifs, one resembling an aggrecanase recognition site. Limited trypsin digestion assays and thermal transition curves imply sequential thermal denaturation of individual triple helical domains of this recombinant collagen, similar to authentic collagen XVI. Molecular images of collagen XVI reveal rod-like molecules which harbor multiple sharp kinks attributing a highly flexible structure presumably introduced by non-collagenous (NC) regions. Terminally located cloverleaf-shaped nodules correspond to the large NC NC11 domain of trimeric collagen XVI. The total length of individual trimeric recombinant collagen XVI molecules constitutes about 240 nm as calculated by atomic force and negative staining electron microscopy. Recombinant collagen XVI interacts with fibrillin-1 and with fibronectin indicating multiple molecular interactions in which this ubiquitously expressed and versatile FACIT-collagen can participate. In vitro generated collagen XVI provides an indispensable tool for future determination of its function during supramolecular assembly of matrix aggregates and its role in maintenance, organization and interaction of fibrillar structures.
J Mol Biol 2004 Jun 11
PMID:Molecular structure and interaction of recombinant human type XVI collagen. 1516 54

Collagen V is a minor component of the heterotypic I/III/V collagen fibrils and the defective product in most cases of classical Ehlers Danlos syndrome (EDS). The present study was undertaken to elucidate the impact of collagen V mutations on skin development, the most severely affected EDS tissues, using mice harboring a targeted deletion of the alpha2(V) collagen gene (Col5a2). Contrary to the original report, our studies indicate that the Col5a2 deletion (a.k.a. the pN allele) represents a functionally null mutation that affects matrix assembly through a complex sequence of events. First the mutation impairs assembly and/or secretion of the alpha1(V)(2)alpha2(V) heterotrimer with the result that the alpha1(V) homotrimer is the predominant species deposited into the matrix. Second, the alpha1(V) homotrimer is excluded from incorporation into the heterotypic collagen fibrils and this in turn severely impairs matrix organization. Third, the mutant matrix stimulates a compensatory loop by the alpha1(V) collagen gene that leads to additional deposition of alpha1(V) homotrimers. These data therefore underscore the importance of the collagen V heterotrimer in dermal fibrillogenesis. Furthermore, reduced thickness of the basement membranes underlying the epidermis and increased apoptosis of the stromal fibroblasts in pN/pN skin strongly indicate additional roles of collagen V in the development of a functional skin matrix.
Mol Cell Biol 2004 Jul
PMID:Development of a functional skin matrix requires deposition of collagen V heterotrimers. 1519 58

A major component of the vessel wall of large arteries and veins is the extracellular matrix (ECM), which consists of collagens, elastin, and proteoglycans. Collagen type I is one of the most abundant of the ECM proteins. We have previously shown that the pro-collagen type I alpha 2 gene contains an enhancer which confers tissue-specific expression in the majority of collagen-producing cells, including blood vessels. In this paper, we delineate a specific vascular smooth muscle cell (vSMC) element: a 100-bp sequence around -16.6 kb upstream of the transcription start site that regulates collagen expression exclusively in vSMCs. Furthermore, we show that the expression is activated through the binding of the homeodomain protein Nkx2.5, which is further potentiated in the presence of GATA6. In contrast, this element was repressed by the binding of the zinc-finger protein deltaEF1/ZEB1. We propose a model of regulation where the activating transcription factor Nkx2.5 and the repressor deltaEF1/ZEB1 compete for an overlapping DNA binding site. This element is important in understanding the molecular mechanisms of vessel remodeling and is a potential target for intervention in vascular diseases where there is excessive deposition of collagen in the vessel wall.
Mol Cell Biol 2004 Jul
PMID:Regulation of collagen type I in vascular smooth muscle cells by competition between Nkx2.5 and deltaEF1/ZEB1. 1522 19


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