GLYCOSYLATION CHANGE ENHANCES MULTIMERIZATION AND COLLAGEN BINDING OF VITRONECTIN, AN EXTRACELLULAR MATRIX GLYCOPROTEIN THAT IS INVOLVED IN TISSUE REMODELING

2002 ◽  
Author(s):  
Kimie Asanuma ◽  
Haruko Ogawa
Keyword(s):  
Extracellular Matrix ◽  
Tissue Remodeling ◽  
Collagen Binding ◽  
Glycosylation Change

scholarly journals Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis

2016 ◽  
Vol 245 (3) ◽  
pp. 351-360 ◽  
Author(s):  
Ilea T. Swinehart ◽  
Stephen F. Badylak
Keyword(s):  
Extracellular Matrix ◽  
Tissue Remodeling

scholarly journals Collagen‐Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis

2021 ◽  
Author(s):  
Martin Ezeani ◽  
Asif Noor ◽  
Karen Alt ◽  
Sean Lal ◽  
Paul S. Donnelly ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Imaging ◽  
Cardiac Fibrosis ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Cyclic Peptide ◽  
Ex Vivo ◽  
Matrix Metalloproteinase 2 ◽  
Collagen Binding ◽  
Matrix Expansion

Background Cardiac fibrosis is the excessive deposition of extracellular matrix in the heart, triggered by a cardiac insult, aging, genetics, or environmental factors. Molecular imaging of the cardiac extracellular matrix with targeted probes could improve diagnosis and treatment of heart disease. However, although this technology has been used to demonstrate focal scarring arising from myocardial infarction, its capacity to demonstrate extracellular matrix expansion and diffuse cardiac fibrosis has not been assessed. Methods and Results Here, we report the use of collagen‐targeted peptides labeled with near‐infrared fluorophores for the detection of diffuse cardiac fibrosis in the β2‐AR (β‐2‐adrenergic receptor) overexpressing mouse model and in ischemic human hearts. Two approaches were evaluated, the first based on a T peptide that binds matrix metalloproteinase‐2‐proteolyzed collagen IV, and the second on the cyclic peptide EP‐3533, which targets collagen I. The systemic and cardiac uptakes of both peptides (intravenously administered) were quantified ex vivo by near‐infrared imaging of whole organs, tissue sections, and heart lysates. The peptide accumulation profiles corresponded to an immunohistochemically‐validated increase in collagen types I and IV in hearts of transgenic mice versus littermate controls. The T peptide could encouragingly demonstrate both the intermediate (7 months old) and severe (11 months old) cardiomyopathic phenotypes. Co‐immunostainings of fluorescent peptides and collagens, as well as reduced collagen binding of a control peptide, confirmed the collagen specificity of the tracers. Qualitative analysis of heart samples from patients with ischemic cardiomyopathy compared with nondiseased donors supported the collagen‐enhancement capabilities of these peptides also in the clinical settings. Conclusions Together, these observations demonstrate the feasibility and translation potential of molecular imaging with collagen‐binding peptides for noninvasive imaging of diffuse cardiac fibrosis.

scholarly journals TGF-β1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hae-Ji Kim ◽  
Joo-Hoo Park ◽  
Jae-Min Shin ◽  
Hyun-Woo Yang ◽  
Heung-Man Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathway ◽  
Chronic Rhinosinusitis ◽  
Molecular Mechanisms ◽  
Tissue Remodeling ◽  
Functional Assay ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Fibroblast Migration ◽  
Tgf Β1

Abstract HSP47 is required for the production of collagen and serves an important role in tissue remodeling, a pathophysiologic mechanism of chronic rhinosinusitis (CRS). We investigated the relationship between HSP47 expression and tissue remodeling in CRS. We also determined the underlying molecular mechanisms of TGF-β1-induced HSP47 and extracellular matrix (ECM) production in nasal fibroblasts. HSP47, α-SMA, fibronectin, and collagen type I expression levels were measured using real-time PCR, western blotting, and immunofluorescence staining. Fibroblast migration was analyzed using scratch and transwell migration assays. Contractile activity was measured with a collagen gel contraction assay. HSP47 is increased in patients with CRS without nasal polyps. TGF-β1 induced HSP47 expression in nasal fibroblasts. Myofibroblast differentiation and ECM production, which are induced by TGF-β1, were inhibited by siHSP47. We also confirmed that the Smad2/3 signaling pathway is involved in TGF-β1-induced HSP47 expression in nasal fibroblasts. In a functional assay, TGF-β1-enhanced migration and contraction ability were inhibited by HSP47 knockout. Glucocorticoid reversed the stimulatory effects of TGF-β1 on HSP47 expression and ECM production in nasal fibroblasts and ex vivo organ cultures. HSP47 expression is involved in TGF-β1-induced myofibroblast differentiation and ECM production through the Smad2/3 signaling pathway, which might contribute to tissue remodeling in chronic rhinosinusitis.

Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis

2021 ◽  
Author(s):  
Yuanxin Zhai ◽  
Quanwei Wang ◽  
Zhanchi Zhu ◽  
Wenlong Zheng ◽  
Sancheng Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Binding Domain ◽  
Collagen Binding ◽  
Cell Behaviors ◽  
Biomedical Material ◽  
Domain Peptide ◽  
Multifunctional Nanocarriers

Abstract Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs. 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs. 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.

scholarly journals SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway.

1993 ◽  
Vol 121 (6) ◽  
pp. 1433-1444 ◽  
Author(s):  
P M Tremble ◽  
T F Lane ◽  
E H Sage ◽  
Z Werb
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Tissue Remodeling ◽  
Synovial Fibroblasts ◽  
Collagen Type Iv ◽  
Secreted Protein ◽  
Type Iv ◽  
Fibronectin Fragments ◽  
Domain Iii ◽  
In Cells

SPARC (osteonectin/BM40) is a secreted protein that modifies the interaction of cells with extracellular matrix (ECM). When we added SPARC to cultured rabbit synovial fibroblasts and analyzed the secreted proteins, we observed an increase in the expression of three metalloproteinases--collagenase, stromelysin, and the 92-kD gelatinase--that together can degrade both interstitial and basement membrane matrices. We further characterized the regulation of one of these metalloproteinases, collagenase, and showed that both collagenase mRNA and protein are upregulated in fibroblasts treated with SPARC. Experiments with synthetic SPARC peptides indicated that a region in the neutral alpha-helical domain III of the SPARC molecule, which previously had no described function, was involved in the regulation of collagenase expression by SPARC. A sequence in the carboxyl-terminal Ca(2+)-binding domain IV exhibited similar activity, but to a lesser extent. SPARC induced collagenase expression in cells plated on collagen types I, II, III, and V, and vitronectin, but not on collagen type IV. SPARC also increased collagenase expression in fibroblasts plated on ECM produced by smooth muscle cells, but not in fibroblasts plated on a basement membrane-like ECM from Engelbreth-Holm-Swarm sarcoma. Collagenase was induced within 4 h in cells treated with phorbol diesters or plated on fibronectin fragments, but was induced after 8 h in cells treated with SPARC. A number of proteins were transiently secreted by SPARC-treated cells within 6 h of treatment. Conditioned medium that was harvested from cultures 7 h after the addition of SPARC, and depleted of residual SPARC, induced collagenase expression in untreated fibroblasts; thus, part of the regulation of collagenase expression by SPARC appears to be indirect and proceeds through a secreted intermediate. Because the interactions of cells with ECM play an important role in regulation of cell behavior and tissue morphogenesis, these results suggest that molecules like SPARC are important in modulating tissue remodeling and cell-ECM interactions.

scholarly journals Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model

2016 ◽  
Vol 1 (1-2) ◽  
pp. 32-44 ◽  
Author(s):  
Jessica L. Ungerleider ◽  
Todd D. Johnson ◽  
Melissa J. Hernandez ◽  
Dean I. Elhag ◽  
Rebecca L. Braden ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tissue Remodeling ◽  
Hindlimb Ischemia

scholarly journals Extracellular Matrix Degradation and Tissue Remodeling in Periprosthetic Loosening and Osteolysis: Focus on Matrix Metalloproteinases, Their Endogenous Tissue Inhibitors, and the Proteasome

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Spyros A. Syggelos ◽  
Alexios J. Aletras ◽  
Ioanna Smirlaki ◽  
Spyros S. Skandalis
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Molecular Mechanisms ◽  
Total Joint Replacement ◽  
Proteolytic Enzymes ◽  
Tissue Remodeling ◽  
Wear Particle ◽  
Matrix Degradation ◽  
Tissue Inhibitors ◽  
Extracellular Matrix Degradation

The leading complication of total joint replacement is periprosthetic osteolysis, which often results in aseptic loosening of the implant, leading to revision surgery. Extracellular matrix degradation and connective tissue remodeling around implants have been considered as major biological events in the periprosthetic loosening. Critical mediators of wear particle-induced inflammatory osteolysis released by periprosthetic synovial cells (mainly macrophages) are inflammatory cytokines, chemokines, and proteolytic enzymes, mainly matrix metalloproteinases (MMPs). Numerous studies reveal a strong interdependence of MMP expression and activity with the molecular mechanisms that control the composition and turnover of periprosthetic matrices. MMPs can either actively modulate or be modulated by the molecular mechanisms that determine the debris-induced remodeling of the periprosthetic microenvironment. In the present study, the molecular mechanisms that control the composition, turnover, and activity of matrix macromolecules within the periprosthetic microenvironment exposed to wear debris are summarized and presented. Special emphasis is given to MMPs and their endogenous tissue inhibitors (TIMPs), as well as to the proteasome pathway, which appears to be an elegant molecular regulator of specific matrix macromolecules (including specific MMPs and TIMPs). Furthermore, strong rationale for potential clinical applications of the described molecular mechanisms to the treatment of periprosthetic loosening and osteolysis is provided.

scholarly journals A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hui Liang ◽  
Xiaoran Li ◽  
Bin Wang ◽  
Bing Chen ◽  
Yannan Zhao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Antibody Fragment ◽  
Collagen Binding ◽  
Egfr Antibody
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