Evaluation of the Cell Specificity and Sulfate Dependence of Glomerular Extracellular Matrix Proteoglycan Synthesis

1995 ◽  
Vol 321 (1) ◽  
pp. 83-93 ◽  
Author(s):  
G.Q. Shen ◽  
G. Kresbach ◽  
M.J. Spiro ◽  
R.G. Spiro
Keyword(s):  
Extracellular Matrix ◽  
Proteoglycan Synthesis ◽  
Cell Specificity ◽  
Glomerular Extracellular Matrix

scholarly journals Glomerular Extracellular Matrix Components and Integrins

1998 ◽  
Vol 5 (3) ◽  
pp. 177-192 ◽  
Author(s):  
Lotus M. Th Sterk ◽  
Annemieke A. De Melker ◽  
Duco Kramer ◽  
Ingrid Kuikman ◽  
Anwar Chand ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Glomerular Extracellular Matrix

scholarly journals Characterization of glomerular extracellular matrix in IgA nephropathy by proteomic analysis of laser-captured microdissected glomeruli

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Flavia Teodora Ioana Paunas ◽  
Kenneth Finne ◽  
Sabine Leh ◽  
Tarig Al-Hadi Osman ◽  
Hans-Peter Marti ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Iga Nephropathy ◽  
Matrix Protein ◽  
Fold Change ◽  
Matrix Metalloproteinase 2 ◽  
Extracellular Matrix Protein ◽  
Glomerular Sclerosis ◽  
Matrix Expansion ◽  
Glomerular Extracellular Matrix

Abstract Background IgA nephropathy (IgAN) involves mesangial matrix expansion, but the proteomic composition of this matrix is unknown. The present study aimed to characterize changes in extracellular matrix in IgAN. Methods In the present study we used mass spectrometry-based proteomics in order to quantitatively compare protein abundance between glomeruli of patients with IgAN (n = 25) and controls with normal biopsy findings (n = 15). Results Using a previously published paper by Lennon et al. and cross-referencing with the Matrisome database we identified 179 extracellular matrix proteins. In the comparison between IgAN and controls, IgAN glomeruli showed significantly higher abundance of extracellular matrix structural proteins (e.g periostin, vitronectin, and extracellular matrix protein 1) and extracellular matrix associated proteins (e.g. azurocidin, myeloperoxidase, neutrophil elastase, matrix metalloproteinase-9 and matrix metalloproteinase 2). Periostin (fold change 3.3) and azurocidin (3.0) had the strongest fold change between IgAN and controls; periostin was also higher in IgAN patients who progressed to ESRD as compared to patients who did not. Conclusion IgAN is associated with widespread changes of the glomerular extracellular matrix proteome. Proteins important in glomerular sclerosis or inflammation seem to be most strongly increased and periostin might be an important marker of glomerular damage in IgAN.

scholarly journals Pathobiochemistry of arthrofibrotic remodeling

2017 ◽  
Vol 5 (4_suppl4) ◽  
pp. 2325967117S0015
Author(s):  
Isabel Faust ◽  
Philipp Traut ◽  
Cornelius Knappe ◽  
Doris Hendig
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Fibrosis ◽  
Mechanical Strain ◽  
Inflammatory Cells ◽  
Scar Tissue ◽  
Proteoglycan Synthesis ◽  
Synthesis Rate ◽  
Matrix Remodeling ◽  
Therapeutic Approaches ◽  
Extracellular Matrix Components

Aims and Objectives: Arthrofibrosis is defined as painful impairment of joint flexibility due to fibrotic tissue remodeling after joint trauma or surgery. The incidence of arthrofibrosis after knee replacement surgery is 5 to 10%. Although conventional therapeutic approaches as for instance mobilization and physiotherapy are applied, an effective and causative therapeutic regimen is not known. Materials and Methods: To characterize arthrofibrotic remodeling of the extracellular matrix, to develop new therapeutic approaches and to define diagnostic biomarkers and therapeutic targets, understanding of biochemical principles is urgently required. Fibrotic remodeling was described in several tissues, whereas synovial fibrosis is one of the least investigated fibrotic disorders. Nevertheless, molecular key events in fibrosis seem to be the same and are initiated by exogenic or endogenic tissue damage and differentiation of resident fibroblasts of the connective tissue to myofibroblasts. Known inductors of myofibroblast differentiation are fibrotic growth factors, which are secreted by platelets, damaged tissue and inflammatory cells, as well as mechanical strain. Research studies concerning cardiac fibrosis in tako-tsubo cardiomyopathy also define emotional stress and sympathicotonic destabilization as profibrotic stressors. Myofibroblasts generate contractile forces and synthesize extracellular matrix components, so that scar tissue accumulates. While myofibroblasts disappear by apoptosis in physiological wound healing, they persist in fibrosis. Results: Recently, we could demonstrate that increased expression of human xylosyltransferase (XT)-I, an enzyme which catalyzes the rate limiting step in proteoglycan glycosylation, is linked to abnormal extracellular matrix remodeling. Serum XT activity reflects proteoglycan synthesis rate and is known as fibrosis biomarker in liver fibrosis or scleroderma. Our data also indicate that XT-I is a cellular key mediator of arthrofibrosis. However, we suggest that molecular changes based on arthrofibrosis are, due to local restriction of the affected joint by the blood-synovial-barrier, not detectable in human serum. Currently, we study synovial XT activity of arthrofibrosis patients and controls in a multicenter study. Conclusion: In summary, we give insights into the complex pathobiochemistry of arthrofibrosis as well as current research projects. A deeper characterization of the involved mechanisms might not only contribute to control and inhibit fibrotic remodeling by interfering with components of fibrotic signal cascades but also to establish new therapeutic strategies.

scholarly journals Gene expression and extracellular matrix ultrastructure of a mineralizing chondrocyte cell culture system.

1991 ◽  
Vol 112 (3) ◽  
pp. 501-513 ◽  
Author(s):  
L C Gerstenfeld ◽  
W J Landis
Keyword(s):  
Extracellular Matrix ◽  
Culture System ◽  
Time Course ◽  
Collagen Synthesis ◽  
Collagen Type ◽  
Fold Increase ◽  
Proteoglycan Synthesis ◽  
Type Ii ◽  
Collagen Types ◽  
Matrix Mineralization

Conditions were defined for promoting cell growth, hypertrophy, and extracellular matrix mineralization of a culture system derived from embryonic chick vertebral chondrocytes. Ascorbic acid supplementation by itself led to the hypertrophic phenotype as assessed by respective 10- and 15-fold increases in alkaline phosphatase enzyme activity and type X synthesis. Maximal extracellular matrix mineralization was obtained, however, when cultures were grown in a nutrient-enriched medium supplemented with both ascorbic acid and 20 mM beta-glycerophosphate. Temporal studies over a 3-wk period showed a 3-4-fold increase in DNA accompanied by a nearly constant DNA to protein ratio. In this period, total collagen increased from 3 to 20% of the cell layer protein; total calcium and phosphorus contents increased 15-20-fold. Proteoglycan synthesis was maximal until day 12 but thereafter showed a fourfold decrease. In contrast, total collagen synthesis showed a greater than 10-fold increase until day 18, a result suggesting that collagen synthesis was replacing proteoglycan synthesis during cellular hypertrophy. Separate analysis of individual collagen types demonstrated a low level of type I collagen synthesis throughout the 21-d time course. Collagen types II and X synthesis increased during the first 2 wk of culture; thereafter, collagen type II synthesis decreased while collagen type X synthesis continued to rise. Type IX synthesis remained at undetectable levels throughout the time course. The levels of collagen types I, II, IX, and X mRNA and the large proteoglycan core protein mRNA paralleled their levels of synthesis, data indicating pretranslational control of synthesis. Ultrastructural examination revealed cellular and extracellular morphology similar to that for a developing hypertrophic phenotype in vivo. Chondrocytes in lacunae were surrounded by a well-formed extracellular matrix of randomly distributed collagen type II fibrils (approximately 20-nm diam) and extensive proteoglycan. Numerous vesicular structures could be detected. Cultures mineralized reproducibly and crystals were located in extracellular matrices, principally associated with collagen fibrils. There was no clear evidence of mineral association with extracellular vesicles. The mineral was composed of calcium and phosphorus on electron probe microanalysis and was identified as a very poorly crystalline hydroxyapatite on electron diffraction. In summary, these data suggest that this culture system consists of chondrocytes which undergo differentiation in vitro as assessed by their elevated levels of alkaline phosphatase and type X collagen and their ultrastructural appearance.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Interleukin-1 β regulation of fibroblast proteoglycan synthesis involves a decrease in versican steady-state mRNA levels

1993 ◽  
Vol 294 (2) ◽  
pp. 613-620 ◽  
Author(s):  
E E Qwarnström ◽  
H T Järveläinen ◽  
M G Kinsella ◽  
C O Ostberg ◽  
L J Sandell ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Steady State ◽  
Chondroitin Sulphate ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Three Dimensional ◽  
Proteoglycan Synthesis ◽  
Mrna Levels ◽  
Pronounced Decrease

This study investigates the effects of interleukin (IL)-1 beta on proteoglycan metabolism by fibroblasts surrounded by endogenous extracellular matrix. In both three-dimensional matrix cultures and long-term monolayer cultures IL-1 beta caused a significant decrease in synthesis and deposition of sulphated proteoglycans, but had no effect on release of deposited material. The decrease in synthesis became successively more pronounced, and corresponded to 40-60% of the control after 72 h incubation. The reduction was almost totally accounted for by an effect on the chondroitin ABC-lyase-sensitive proteoglycans. Gel electrophoresis showed a significant decrease in a high-molecular-mass chondroitin ABC-lyase-sensitive proteoglycan after incubation with IL-1 beta. Northern-blot analyses of total RNA revealed a pronounced decrease in the steady-state mRNA levels of versican, the large chondroitin sulphate, with levels corresponding to 10-30% of controls. In comparison, the steady-state mRNA level for decorin, the major sulphated proteoglycan synthesized by the cells, was only slightly affected. The prominent decrease in synthesis of sulphated proteoglycans induced in long-term fibroblast cultures, including the pronounced decrease in versican steady-state mRNA levels, is likely to have a significant effect on the structure of the extracellular matrix. Induction of this type of change may constitute a significant mechanism whereby IL-1 beta can affect the properties of connective tissue during inflammation and wound healing.

scholarly journals Characterization of glomerular extracellular matrix by proteomic analysis of laser-captured microdissected glomeruli

2017 ◽  
Vol 91 (2) ◽  
pp. 501-511 ◽  
Author(s):  
Liliane Hobeika ◽  
Michelle T. Barati ◽  
Dawn J. Caster ◽  
Kenneth R. McLeish ◽  
Michael L. Merchant
Keyword(s):  
Extracellular Matrix ◽  
Proteomic Analysis ◽  
Glomerular Extracellular Matrix

Glomerular extracellular matrix and growth factors in diffuse mesangial sclerosis

2001 ◽  
Vol 16 (5) ◽  
pp. 429-438 ◽  
Author(s):  
Youxin Yang ◽  
Shao-yu Zhang ◽  
Mireille Sich ◽  
Agnès Béziau ◽  
Lambert P. W. J. van den Heuvel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Diffuse Mesangial Sclerosis ◽  
Glomerular Extracellular Matrix
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