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BMC Cancer May 2019Vitronectin is a multifunctional glycoprotein known in several human tumors for its adhesive role in processes such as cell growth, angiogenesis and metastasis. In this...
BACKGROUND
Vitronectin is a multifunctional glycoprotein known in several human tumors for its adhesive role in processes such as cell growth, angiogenesis and metastasis. In this study, we examined vitronectin expression in neuroblastoma to investigate whether this molecule takes part in cell-cell or cell-extracellular matrix interactions that may confer mechanical properties to promote tumor aggressiveness.
METHODS
We used immunohistochemistry and image analysis tools to characterize vitronectin expression and to test its prognostic value in 91 neuroblastoma patients. To better understand the effect of vitronectin, we studied its in vitro expression using commercial neuroblastoma cell lines and in vivo using intra-adrenal gland xenograft models by immunohistochemistry.
RESULTS
Digital image analysis allowed us to associate vitronectin staining intensity and location discriminating between territorial vitronectin and interterritorial vitronectin expression patterns. High territorial vitronectin expression (strong staining associated with pericellular and intracellular location) was present in tumors from patients with metastatic undifferentiating neuroblastoma, that were MYCN amplified, 11q deleted or with segmental chromosomal profiles, in the high-risk stratification group and with high genetic instability. In vitro studies confirmed that vitronectin is expressed in tumor cells as small cytoplasmic dot drops. In vivo experiments revealed tumor cells with high and dense cytoplasmic vitronectin expression.
CONCLUSIONS
These findings highlight the relevance of vitronectin in neuroblastoma tumor biology and suggest its potential as a future therapeutic target in neuroblastoma.
Topics: Animals; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Image Interpretation, Computer-Assisted; Male; Mice; Neoplasm Transplantation; Neuroblastoma; Prognosis; Survival Analysis; Tumor Microenvironment; Up-Regulation; Vitronectin
PubMed: 31117974
DOI: 10.1186/s12885-019-5693-2 -
Journal of Stem Cells & Regenerative... 2022Coronary heart disease (CHD) is a leading cause of death globally, while its current management is limited to reducing the myocardial infarction area without actually...
Coronary heart disease (CHD) is a leading cause of death globally, while its current management is limited to reducing the myocardial infarction area without actually replacing dead cardiomyocytes. Direct cell reprogramming is a method of cellular cardiomyoplasty which aims for myocardial tissue regeneration, and CD34 cells are one of the potential sources due to their shared embryonic origin with cardiomyocytes. However, the isolation and culture of non-adherent CD34 cells is crucial to obtain adequate cells for high-efficiency genetic modification. This study aimed to investigate the optimal method for isolation and culture of CD34 peripheral blood cells using certain culture media. A peripheral blood sample was obtained from a healthy subject and underwent pre-enrichment, isolation, and expansion. The culture was subsequently observed for their viability, adherence, and confluence. Day 0 observation of the culture showed a healthy CD34 cell with a round cell shape, without any adherent cells present yet. Day 4 of observation showed that CD34 cells within the blood plasma medium became adherent, indicated by their transformations into spindle or oval morphologies. Meanwhile, CD34 cells in vitronectin and fibronectin media showed no adherent cells and many of them died. Day 7 observation revealed more adherent CD34 cells in blood plasma medium, and which had 75% of confluence. In conclusion, the CD34 cells that were isolated using a combination of density and magnetic methods may be viable and adequately adhere in culture using blood plasma medium, but not in cultures using fibronectin and vitronectin.
PubMed: 36003658
DOI: 10.46582/jsrm.1801004 -
FEBS Letters Aug 2020Pathogens that colonize deep tissues and spread systemically encounter the innate host resistance mechanism of complement-mediated lysis and complement opsonization... (Review)
Review
Pathogens that colonize deep tissues and spread systemically encounter the innate host resistance mechanism of complement-mediated lysis and complement opsonization leading to engulfment and degradation by phagocytic cells. Yersinia and Salmonella species have developed numerous strategies to block the antimicrobial effects of complement. These include recruitment of complement regulatory proteins factor H, C4BP, and vitronectin (Vn) as well as interference in late maturation events such as assembly of C9 into the membrane attack complex that leads to bacterial lysis. This review will discuss the contributions of various surface structures (proteins, lipopolysaccharide, and capsules) to evasion of complement-mediated immune clearance of the systemic pathogens Yersiniae and Salmonellae. Bacterial proteins required for recruitment of complement regulatory proteins will be described, including the details of their interaction with host regulatory proteins, where known. The potential role of the surface proteases Pla (Yersinia pestis) and PgtE (Salmonella species) on the activity of complement regulatory proteins will also be addressed. Finally, the implications of complement inactivation on host cell interactions and host cell targeting for type 3 secretion will be discussed.
Topics: Animals; Bacterial Proteins; Complement System Proteins; Humans; Immune Evasion; Plasminogen Activators; Salmonella; Type III Secretion Systems; Yersinia pestis
PubMed: 32170725
DOI: 10.1002/1873-3468.13771 -
Cells May 2022The pathogenesis of age-related macular degeneration (AMD), a frequent disorder of the central retina, is incompletely understood. Genome-wide association studies (GWAS)...
The pathogenesis of age-related macular degeneration (AMD), a frequent disorder of the central retina, is incompletely understood. Genome-wide association studies (GWAS) suggest a strong contribution of genomic variation in AMD susceptibility. Nevertheless, little is known about biological mechanisms of the disease. We reported previously that the AMD-associated polymorphism rs704C > T in the vitronectin (VTN) gene influences protein expression and functional aspects of encoded vitronectin, a human blood and extracellular matrix (ECM) protein. Here, we refined the association of rs704 with AMD in 16,144 cases and 17,832 controls and noted that rs704 is carried exclusively by the neovascular AMD subtype. Interaction studies demonstrate that rs704 affects the ability of vitronectin to bind the angiogenic regulator plasminogen activator inhibitor 1 (PAI-1) but has no influence on stabilizing its active state. Western blot analysis and confocal imaging reveal a strong enrichment of PAI-1 in the ECM of cultured endothelial cells and RPE cell line ARPE-19 exposed to vitronectin. Large-scale gene expression of VTN and PAI-1 showed positive correlations and a statistically significant increase in human retinal and blood tissues aged 60 years and older. Our results suggest a mechanism by which the AMD-associated rs704 variant in combination with ageing may contribute to the vascular complications in AMD.
Topics: Aged; Angiogenesis Inhibitors; Endothelial Cells; Genome-Wide Association Study; Humans; Macular Degeneration; Middle Aged; Plasminogen Activator Inhibitor 1; Vascular Endothelial Growth Factor A; Visual Acuity; Vitronectin
PubMed: 35681461
DOI: 10.3390/cells11111766 -
Molecules (Basel, Switzerland) Dec 2022In orthopedic, dental, and maxillofacial fields, joint prostheses, plates, and screws are widely used in the treatment of problems related to bone tissue. However, the...
In orthopedic, dental, and maxillofacial fields, joint prostheses, plates, and screws are widely used in the treatment of problems related to bone tissue. However, the use of these prosthetic systems is not free from complications: the fibrotic encapsulation of endosseous implants often prevents optimal integration of the prostheses with the surrounding bone. To overcome these issues, biomimetic titanium implants have been developed where synthetic peptides have been selectively grafted on titanium surfaces via Schiff base formation. We used the retro-inverted sequence (DHVPX) from [351-359] human Vitronectin and its dimer (D2HVP). Both protease-resistant peptides showed increased human osteoblast adhesion and proliferation, an augmented number of focal adhesions, and cellular spreading with respect to the control. D2HVP-grafted samples significantly enhance Secreted Phosphoprotein 1, Integrin Binding Sialoprotein, and Vitronectin gene expression vs. control. An estimation of peptide surface density was determined by Two-photon microscopy analysis on a silanized glass model surface labeled with a fluorescent analog.
Topics: Humans; Cell Adhesion; Vitronectin; Titanium; Peptide Hydrolases; Peptides; Osteoblasts; Endopeptidases; Surface Properties
PubMed: 36557865
DOI: 10.3390/molecules27248727 -
Research in Microbiology 2017A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane....
A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane. Surface-anchored leptospiral enolase displays plasminogen binding activity. In this work, we explored the consequences of this interaction and also assessed whether Leptospira enolase might display additional moonlighting functions by interacting with other host effector proteins. We first demonstrated that enolase-bound plasminogen is converted to its active form, plasmin. The protease plasmin targets human fibrinogen and vitronectin, but not the complement proteins C3b and C5. Leptospira enolase also acts as an immune evasion protein by interacting with the negative complement regulators C4b binding protein and factor H. Once bound to enolase, both regulators remain functional as cofactors of factor I, mediating cleavage of C4b and C3b. In conclusion, enolase may facilitate leptospiral survival and dissemination, thus contributing to bacterial virulence. The identification and characterization of moonlighting proteins is a growing field of bacterial pathogenesis, as these multifaceted proteins may represent potential future therapeutic targets to fight bacterial infections.
Topics: Bacterial Proteins; Complement C3b; Complement C4b-Binding Protein; Complement C5; Complement Factor H; Fibrinolysin; Humans; Immune Evasion; Leptospira; Phosphopyruvate Hydratase; Plasminogen; Protein Binding
PubMed: 27989763
DOI: 10.1016/j.resmic.2016.10.005 -
Animals : An Open Access Journal From... Aug 2019Vitronectin plays a role in the blood homeostasis and has been implicated in cell adhesion, migration, and proliferation. Vitronectin has a potential role affecting the...
Vitronectin plays a role in the blood homeostasis and has been implicated in cell adhesion, migration, and proliferation. Vitronectin has a potential role affecting the residual feed intake (RFI) or feeding efficiency in swine production. Its variations have not been reported in Chinese swine breeds. In this study, two regions of porcine vitronectin were analyzed using PCR and sequencing. The sequence analysis revealed thirteen nucleotide substitutions in region 1 (exon 2- exon 3) and three nucleotide substitutions in region 2 (exon 5- intron 5), which would result in five amino acid changes (p.Ala52Thr, p.Leu94Pro, p.Leu94Gln, p.Gln94Pro, and p.Glu126Gly). In region 1, c.156C/T, c.281A/T, and c.377A/G were the most common (at a total frequency of 49.3%, 31.3% and 31.9% respectively), whereas c.153C/T and c.180C/G were rare (at a total frequency of 1.39%). In region 2, c.597 + 12A/G was the most common (at a total frequency of 39.6%), followed by c.597 + 15A/G (at a total frequency of 31.3%) and c.459A/G (at a total frequency of 16.0%). There was a difference ( < 0.05) in variant frequencies between Chinese breeds and overseas breeds. These results indicate that the porcine vitronectin gene is polymorphic and suggest further analysis is required to see if the variation detected affects RFI or feed efficiency in swines.
PubMed: 31382414
DOI: 10.3390/ani9080520 -
Protein Science : a Publication of the... Nov 2016Proteins and their modifications of the natural mummy of Cangrande della Scala (Prince of Verona, Northern Italy, 1291-1329) were studied. The nano-LC-Q-TOF analysis of...
Proteins and their modifications of the natural mummy of Cangrande della Scala (Prince of Verona, Northern Italy, 1291-1329) were studied. The nano-LC-Q-TOF analysis of samples of rib bone and muscle from the mummy showed the presence of different proteins including Types I, III, IV, V, and XI collagen, hemoglobin (subunits alpha and beta), ferritin, biglycan, vitronectin, prothrombin, and osteocalcin. The structure of Type I and Type III collagen was deeply studied to evaluate the occurrence of modifications in comparison with Type I and Type III collagen coming from tissues of recently died people. This analysis showed high percentage of asparaginyl and glutaminyl deamidation, carbamylation and carboxymethylation of lysine, as well as oxidation and dioxidation of methionine. The most common reaction during the natural mummification process was oxidation-the majority of lysine and proline of collagen Type I was hydroxylated whereas methionine was oxidated (oxidated or dioxidated). To the best of our knowledge, this is the first study which reports the protein profile of a natural mummified human tissue and the first one which describes the carbamylation and carboxymethylation of lysine in mummified tissues.
Topics: Collagen; Hemoglobins; History, Medieval; Humans; Mummies; Protein Processing, Post-Translational
PubMed: 27543755
DOI: 10.1002/pro.3024 -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
OBJECTIVE
The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
METHODS
This study was conducted between September 2020 and December 2020 at the University of Health Sciences, Bursa Yuksek Ihtisas Research and Training Hospital, Department of Obstetrics and Gynecology. A total of 30 pregnant women with gestational diabetes mellitus and 60 healthy controls between 24 and 27/6 weeks of gestation were included. The inclusion criteria were as follows: being between 18 and 45 years old and 24-27/6 gestational weeks, having singleton pregnancy, diagnosed with gestational diabetes mellitus by using a two-step challenge test. The exclusion criteria of this study were as follows: chronic inflammatory or infectious disease, fasting blood glucose>126 mg/dL, intolerance to glucose tolerance testing, abnormal liver or kidney function tests, as well as pregnancy with pre-gestational diabetes history of adverse perinatal outcomes. Serum vitronectin and plasminogen activator inhibitor-1 levels were measured using the enzyme-linked immunosorbent assay method.
RESULTS
Vitronectin and plasminogen activator inhibitor-1 levels were higher in the gestational diabetes mellitus group compared with controls [91.85 (23.08) vs. 80.10 (39.18) ng/mL, for vitronectin and 6.50 (1.05) vs. 4.35(1.0) ng/mL, for plasminogen activator inhibitor-1 (for both p<0.001)]. vitronectin >84.7 ng/mL was found to predict gestational diabetes mellitus with a sensitivity of 70% and specificity of 63.3%. Moreover, vitronectin had a significant positive correlation with fasting blood glucose (r=0.476, p<0.001), postprandial blood glucose (r=0.489, p<0.001), HbA1c (r=0.713, p<0.001), and plasminogen activator inhibitor-1 (r=0.586, p<0.001).
CONCLUSION
This study revealed that second-trimester vitronectin and plasminogen activator inhibitor-1 are increased in gestational diabetes mellitus and vitronectin could be a candidate for the prediction of gestational diabetes mellitus.
Topics: Pregnancy; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Diabetes, Gestational; Vitronectin; Blood Glucose; Enzyme-Linked Immunosorbent Assay; Exercise Test
PubMed: 37729377
DOI: 10.1590/1806-9282.20230563 -
Scientific Reports Jun 2024Cellular senescence plays a role in the development of aging-associated degenerative diseases. Cell therapy is recognized as a candidate treatment for degenerative...
Cellular senescence plays a role in the development of aging-associated degenerative diseases. Cell therapy is recognized as a candidate treatment for degenerative diseases. To achieve the goal of cell therapy, the quality and good characteristics of cells are concerned. Cell expansion relies on two-dimensional culture, which leads to replicative senescence of expanded cells. This study aimed to investigate the effect of cell culture surface modification using fibronectin (FN) and vitronectin (VN) in adipose-derived stem cells (ADSCs) during long-term expansion. Our results showed that ADSCs cultured in FN and VN coatings significantly enhanced adhesion, proliferation, and slow progression of cellular senescence as indicated by lower SA-β-gal activities and decreased expression levels of genes including p16, p21, and p53. The upregulation of integrin α5 and αv genes influences phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), and AKT proteins. FN and VN coatings upregulated AKT and MDM2 leading to p53 degradation. Additionally, MDM2 inhibition by Nutlin-3a markedly elevated p53 and p21 expression, increased cellular senescence, and induced the expression of inflammatory molecules including HMGB1 and IL-6. The understanding of FN and VN coating surface influencing ADSCs, especially senescence characteristics, offers a promising and practical point for the cultivation of ADSCs for future use in cell-based therapies.
Topics: Vitronectin; Cellular Senescence; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Fibronectins; Proto-Oncogene Proteins c-mdm2; Humans; Signal Transduction; Cells, Cultured; Stem Cells; Cell Proliferation; Adipose Tissue; Cell Culture Techniques
PubMed: 38902430
DOI: 10.1038/s41598-024-65339-z