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

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.

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 Functional Analysis of the Collagen Binding Proteins of Streptococcus parasanguinis FW213

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Yi-Ywan M. Chen ◽  
Pei-Hua Tsai ◽  
Zong-Sian Ye ◽  
Yu-Wen Huang ◽  
Hui-Ru Shieh ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Binding Proteins ◽  
Type I Collagen ◽  
Galleria Mellonella ◽  
Opportunistic Pathogen ◽  
Type I ◽  
Collagen Binding ◽  
Content Type ◽  
Extracellular Matrix Molecules ◽  
Streptococcus Parasanguinis

ABSTRACT Streptococcus parasanguinis is a dominant isolate of dental plaque and an opportunistic pathogen associated with subacute endocarditis. As the expression of collagen binding proteins (CBPs) could promote the establishment of S. parasanguinis in the host, the functions of three putative CBP-encoding loci, Spaf_0420, Spaf_1570, and Spaf_1573, were analyzed using isogenic mutant strains. It was revealed that S. parasanguinis FW213 bound effectively to fibronectin and type I collagen, but the strain’s affinity for laminin and type IV collagen was quite low. By using various deletion derivatives, it was found that these three loci mediated the binding of S. parasanguinis to multiple extracellular matrix molecules, with type I collagen as the common substrate. Derivative strains with a deletion in any of the three loci expressed reduced binding to trypsin-treated swine heart valves. The deletion of these loci also reduced the viable count of S. parasanguinis bacteria within macrophages, especially the loss of Spaf_0420, but only strains with deletions in Spaf_0420 and Spaf_1570 expressed reduced virulence in the Galleria mellonella larva model. The deletion of Spaf_1570 and Spaf_1573 affected mainly the structure, but not the overall mass, of biofilm cultures in a flow cell system. Thus, CBPs are likely to be more critical for the initial colonization of S. parasanguinis on host tissues during the development of endocarditis. IMPORTANCE Bacteria generally can utilize multiple adhesins to establish themselves in the host. We found that Streptococcus parasanguinis, a dominant oral commensal and an opportunistic pathogen for subacute endocarditis, possesses at least three collagen-binding proteins that enable S. parasanguinis to successfully colonize damaged heart tissues and escape innate immune clearance. The binding specificities of these three proteins for extracellular matrix molecules differ, although all three proteins participate in biofilm formation by S. parasanguinis. The “multiligand for multisubstrate” feature of these adhesins may explain the high adaptability of this microbe to different tissue sites.

scholarly journals Diversity of ace, a Gene Encoding a Microbial Surface Component Recognizing Adhesive Matrix Molecules, from Different Strains of Enterococcus faecalis and Evidence for Production of Ace during Human Infections

2000 ◽  
Vol 68 (9) ◽  
pp. 5210-5217 ◽  
Author(s):  
Sreedhar R. Nallapareddy ◽  
Kavindra V. Singh ◽  
Ruay-Wang Duh ◽  
George M. Weinstock ◽  
Barbara E. Murray
Keyword(s):  
Amino Acids ◽  
Extracellular Matrix ◽  
Amino Acid ◽  
Enterococcus Faecalis ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Rabbit Serum ◽  
Collagen Types ◽  
Collagen Binding ◽  
Different Strains

ABSTRACT Our previous work reported that most Enterococcus faecalis strains adhered to the extracellular matrix proteins collagen types I and IV and laminin after growth at 46°C, but not 37°C, and we subsequently identified an E. faecalissequence, ace, that encodes a bacterial adhesin similar to the collagen binding protein Cna of Staphylococcus aureus. In this study, we examined the diversity of E. faecalis-specific ace gene sequences among different isolates obtained from various geographic regions as well as from various clinical sources. A comparison of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis strains identified a highly conserved N-terminal A domain, followed by a variable B domain which contains two to five repeats of 47 amino acids in tandem array, preceded by a 20-amino-acid partial repeat. Using 17 other strains collected worldwide, the 5′ region of acethat encodes the A domain was sequenced, and these sequences showed ≥97.5% identity. Among the previously reported five amino acids critical for collagen binding by Cna of S. aureus, four were found to be identical in Ace from all strains tested. Polyclonal immune rabbit serum prepared against recombinant Ace A derived fromE. faecalis strain OG1RF detected Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at 46°C; Ace was detected in four different molecular sizes that correspond to the variation in the B repeat region. To determine if there was any evidence to indicate that Ace might be produced under physiological conditions, we quantitatively assayed sera collected from patients with enterococcal infections for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from patients withE. faecalis endocarditis showed reactivity with titers from 1:32 to >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower titers of antibodies to other E. faecalis antigens as well. Human-derived, anti-Ace A immunoglobulins G purified from an E. faecalis endocarditis patient serum inhibited adherence of 46°C-grown E. faecalis OG1RF to collagen types I and IV and laminin. In conclusion, these results show that ace is highly conserved among isolates of E. faecalis, with at least four variants related to the differences in the B domain, is expressed by different strains during infection in humans, and human-derived antibodies can block adherence to these extracellular matrix proteins.

scholarly journals The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanzhen Yu ◽  
Xingzhi Liu ◽  
Zhe Zhao ◽  
Zhongjuan Xu ◽  
Yong Qiao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Critical Role ◽  
Host Cells ◽  
Therapeutic Application ◽  
Collagen Binding ◽  
Therapeutic Delivery ◽  
Fibrotic Process ◽  
Low Efficiency

Pulmonary fibrosis (PF) is a severe respiratory disease caused by lung microenvironment changes. TGF-β/Smad3 signaling pathway plays a critical role in the fibrotic process. MicroRNA-29 (miR-29) has proved to alleviate the occurrence of PF by downregulating TGF-β/Smad3 signaling pathway. The miRNA application encounters obstacles due to its low stability in body and no targeting to lesions. Exosomes can be used for therapeutic delivery of miRNA due to their favorable delivery properties. However, low efficiency of separation and production impedes the therapeutic application of exosomes. In this study, we developed a liquid natural extracellular matrix (ECM) enriched with miR-29-loaded exosomes for PF treatment. The collagen-binding domain (CBD)-fused Lamp2b (CBD-Lamp2b) and miR-29 were overexpressed in human foreskin fibroblast (HFF) host cells for the entrapment of miR-29-loaded exosomes in ECM of the cells. The repeated freeze-thaw method was performed to prepare the liquid ECM enriched with exosomes without destroying the exosomal membrane. In summary, this study developed a novel functional ECM biomaterial for therapy of PF, and also provided a promising gene therapy platform for different diseases by treatment with liquid ECM that is, enriched with exosomes loaded with different functional miRNAs.

Collagen-binding VEGF targeting the cardiac extracellular matrix promotes recovery in porcine chronic myocardial infarction

2018 ◽  
Vol 6 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Chunying Shi ◽  
Yannan Zhao ◽  
Yun Yang ◽  
Cheng Chen ◽  
Xianglin Hou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Effective Therapy ◽  
Chronic Myocardial Infarction ◽  
Collagen Binding

An effective therapy for chronic myocardial infarction (MI) has yet to be developed.

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