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Journal of Clinical Research in... May 2024In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. The aim was to...
OBJECTIVE
In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. The aim was to investigate levels of versican and biglycan in obese children and any potential association with body adipose tissue and hepatosteatosis.
METHODS
Serum levels of versican, biglycan, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were measured by ELISA. Fat deposition in the liver, spleen, and subcutaneous adipose tissue was calculated using the IDEAL-IQ sequences in magnetic resonance images. Bioimpedance analysis was performed using the Tanita BC 418 MA device.
RESULTS
The study included 36 obese and 30 healthy children. The age of obese children was 13.6 (7.5-17.9) years, while the age of normal weight children was 13.0 (7.2-17.9) years (p=0.693). Serum levels of versican, hsCRP, and IL-6 were higher in the obese group (p=0.044, p=0.039, p=0.024, respectively), while no significant difference was found in biglycan levels between the groups. There was a positive correlation between versican, biglycan, hsCRP, and IL-6 (r=0.381 p=0.002, r=0.281 p=0.036, rho=0.426 p=0.001, r=0.424 p=0.001, rho=0.305 p=0.017, rho=0.748 p<0.001, respectively). Magnetic resonance imaging revealed higher segmental and global hepatic steatosis in obese children. There was no relationship between hepatic fat content and versican, biglycan, IL-6, and hsCRP. Versican, biglycan, hsCRP, and IL-6 were not predictive of hepatosteatosis. Body fat percentage >32% provided a predictive sensitivity of 81.8% and a specificity of 70.5% for hepatosteatosis [area under the curve (AUC): 0.819, p<0.001]. Similarly, a body mass index standard deviation score >1.75 yielded a predictive sensitivity of 81.8% and a specificity of 69.8% for predicting hepatosteatosis (AUC: 0.789, p<0.001).
CONCLUSION
Obese children have higher levels of versican, hsCRP, and IL-6, and more fatty liver than their healthy peers.
Topics: Humans; Versicans; Child; Male; Female; Biglycan; Adolescent; Adipose Tissue; Pediatric Obesity; Macrophages; Adipocytes; Fatty Liver; Biomarkers; C-Reactive Protein; Interleukin-6; Case-Control Studies
PubMed: 38238969
DOI: 10.4274/jcrpe.galenos.2024.2023-9-18 -
Science Advances Feb 2021Dysregulations in the inflammatory response of the body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and...
Dysregulations in the inflammatory response of the body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and associated with increased severity and mortality. Hence, there is a need for identifying therapeutic targets to modulate this pathological immune response. Here, we propose a single cell-based computational methodology for predicting proteins to modulate the dysregulated inflammatory response based on the reconstruction and analysis of functional cell-cell communication networks of physiological and pathological conditions. We validated the proposed method in 12 human disease datasets and performed an in-depth study of patients with mild and severe symptomatology of the coronavirus disease 2019 for predicting novel therapeutic targets. As a result, we identified the extracellular matrix protein versican and Toll-like receptor 2 as potential targets for modulating the inflammatory response. In summary, the proposed method can be of great utility in systematically identifying therapeutic targets for modulating pathological immune responses.
Topics: COVID-19; Cell Communication; Cytokines; Humans; Immunity, Innate; Immunologic Factors; Inflammation; Lymphocytes; Receptors, Chemokine; SARS-CoV-2; Severity of Illness Index; Systems Biology; Toll-Like Receptor 2; Versicans
PubMed: 33536217
DOI: 10.1126/sciadv.abe5735 -
Comparative Biochemistry and... Dec 2022Ovarian cyclicity is variable in adult Siberian hamsters (Phodopus sungorus), who respond to long breeding season photoperiods with follicle development and ovulation,...
Ovarian cyclicity is variable in adult Siberian hamsters (Phodopus sungorus), who respond to long breeding season photoperiods with follicle development and ovulation, while short photoperiods typical of the non-breeding season induce gonadal atrophy. Recent RNAseq results identified ovarian matrix components and regulators of metabolism as differentially regulated by photoperiod; however, the impact of photoperiod across a full cycle of ovarian regression and recrudescence had not been explored for additional regulators of ovarian metabolism and extracellular matrix components. We hypothesized that matrix and metabolism-related genes would be expressed differentially across photoperiods that mimic breeding and non-breeding season daylengths. Hamsters were housed in one of four photoperiod groups: long day (16 h of light per day: 8 h of dark; LD, controls), short day regressed (8 L:16D; SD, regressed), and females exposed to SD then transferred to LD to stimulate return of ovarian function for 2 (early recrudescence), or 8 (late recrudescence) weeks. Plasma leptin concentrations along with expression of ovarian versican and liver-receptor homolog-1/Nr582 mRNA decreased in SD compared to LD and late recrudescence, while vimentin mRNA expression peaked in early and late recrudescence. Ovarian expression of fibronectin and extracellular matrix protein-1 was low in LD ovaries and increased in regressed and recrudescing groups. Expression of hyaluronidase-2, nectin-2, liver-X receptors-α and-β, and adiponectin mRNA peaked in late recrudescence, with no changes noted for adiponectin receptor-1 and -2. The results offer a first look at the parallels between expression of these genes and the dynamic remodeling that occurs during ovarian regression and recrudescence.
Topics: Adiponectin; Animals; Cricetinae; Extracellular Matrix; Female; Fibronectins; Gene Expression; Hyaluronoglucosaminidase; Leptin; Nectins; Ovary; Phodopus; Photoperiod; RNA, Messenger; Receptors, Adiponectin; Recurrence; Seasons; Versicans; Vimentin
PubMed: 36041709
DOI: 10.1016/j.cbpa.2022.111302 -
The Journal of Histochemistry and... Nov 2021Versican, a chondroitin sulfate proteoglycan, is an essential component of the extracellular matrix (ECM) in inflammatory lung disease. Versican's potential as an...
Versican, a chondroitin sulfate proteoglycan, is an essential component of the extracellular matrix (ECM) in inflammatory lung disease. Versican's potential as an immunomodulatory molecule makes it a promising therapeutic target for controlling host immune responses in the lungs. To establish changes to versican expression and accumulation during influenza A viral pneumonia, we document the temporal and spatial changes to versican mRNA and protein in concert with pulmonary inflammatory cell infiltration. These studies were performed in the lungs of wild-type C57BL6/J mice on days 3, 6, 9, and 12 post-infection with influenza A virus using immunohistochemistry, in situ hybridization, and quantitative digital pathology. Using duplex in situ hybridization, we demonstrate that type I interferon signaling contributes significantly to versican expression in lung stromal cells. Our findings show that versican is a type I interferon-stimulated gene in pulmonary fibroblasts and pericytes in the context of viral pneumonia. These data also provide a guide for future studies to determine the role of versican in the pulmonary immune response to influenza infection.
Topics: Animals; Humans; Influenza, Human; Interferon Type I; Lung; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Stromal Cells; Versicans
PubMed: 34666527
DOI: 10.1369/00221554211054447 -
Cells Jul 2021The lung extracellular matrix (ECM) plays a key role in the normal architecture of the lung, from embryonic lung development to mechanical stability and elastic recoil... (Review)
Review
The lung extracellular matrix (ECM) plays a key role in the normal architecture of the lung, from embryonic lung development to mechanical stability and elastic recoil of the breathing adult lung. The lung ECM can modulate the biophysical environment of cells through ECM stiffness, porosity, topography and insolubility. In a reciprocal interaction, lung ECM dynamics result from the synthesis, degradation and organization of ECM components by the surrounding structural and immune cells. Repeated lung injury and repair can trigger a vicious cycle of aberrant ECM protein deposition, accompanied by elevated ECM stiffness, which has a lasting effect on cell and tissue function. The processes governing the resolution of injury repair are regulated by several pathways; however, in chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary disease (IPF) these processes are compromised, resulting in impaired cell function and ECM remodeling. Current estimates show that more than 60% of the human coding transcripts are regulated by miRNAs. miRNAs are small non-coding RNAs that regulate gene expressions and modulate cellular functions. This review is focused on the current knowledge of miRNAs in regulating ECM synthesis, degradation and topography by cells and their dysregulation in asthma, COPD and IPF.
Topics: Asthma; Collagen; Epithelial Cells; Extracellular Matrix; Fibroblasts; Fibronectins; Gene Expression Regulation; Humans; Idiopathic Pulmonary Fibrosis; Laminin; Lung; MicroRNAs; Myocytes, Smooth Muscle; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Signal Transduction; Syndecans; Versicans
PubMed: 34359876
DOI: 10.3390/cells10071706 -
Ideggyogyaszati Szemle Sep 2020Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited...
BACKGROUND AND PURPOSE
Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness - mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components.
METHODS
Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured.
RESULTS
Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93.
CONCLUSION
The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.
Topics: Biomarkers, Tumor; Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Isocitrate Dehydrogenase; Prognosis; RNA, Messenger; Tumor Suppressor Proteins
PubMed: 33035418
DOI: 10.18071/isz.73.0317 -
European Cells & Materials Jan 2023A critical component of the temporomandibular joint (TMJ) is the fibrocartilage articular disc (AD). Researchers have attempted to regenerate the AD to alleviate TMJ...
A critical component of the temporomandibular joint (TMJ) is the fibrocartilage articular disc (AD). Researchers have attempted to regenerate the AD to alleviate TMJ osteoarthritis but alternative cell sources for use in AD regenerative approaches are needed due to insufficient extracellular matrix (ECM) production by total articular disc cells (TACs). Tissue-specific progenitor cells have been identified in many tissues. The aim of the present study was to identify adult multipotent progenitor cells within the AD suitable for regenerative medicine applications. A novel AD progenitor cell population was identified in rhesus macaques. Clonally derived articular disc progenitor cells (ADPs) were isolated using fibronectin differential cell adhesion. ADPs represent between 1 and 3 % of the TAC population and are capable of in vitro expansion beyond 60 population doublings. ADPs were characterized using osteogenic, adipogenic, and fibrochondrogenesis differentiation assays. Clones exhibited phenotypic plasticity, differentiating into osteocytes, adipocytes, and fibrochondrocytes. ECM secretion profiles following fibrochondrogenic differentiation were assessed using immunohistochemistry (IHC), fluorescently activated cell sorting (FACS), total collagen, and glycosaminoglycan (GAG) assays and compared with TACs, articular cartilage progenitor cells (ACPs), tendon progenitor cells (TPCs) and bone-marrow-derived mesenchymal stem cells (BMMSCs). ADP pellet cultures produced a biochemical phenotype similar to native AD tissue, with production of versican (VCAN) and collagen types I, II, III, and VI (COL1, COL2, COL3, COL6). However, clonally derived ADP cell lines produced different amounts of ECM and exhibited different expansion potentials. These findings indicated flexibility in clone selection for potential regenerative strategies to recapitulate native anisotropy.
Topics: Animals; Macaca mulatta; Stem Cells; Temporomandibular Joint Disc; Temporomandibular Joint; Cartilage, Articular; Cell Differentiation; Clone Cells
PubMed: 36625228
DOI: 10.22203/eCM.v045a01 -
International Journal of Molecular... Apr 2023Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is...
Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.
Topics: Humans; Carcinoma, Transitional Cell; Versicans; Urinary Bladder Neoplasms; Kidney Neoplasms; Biomarkers, Tumor; Urinary Tract
PubMed: 37108649
DOI: 10.3390/ijms24087486 -
The Journal of Biological Chemistry 2021Airway inflammation is a critical feature of lower respiratory tract infections caused by viruses such as respiratory syncytial virus (RSV). A growing body of literature...
Airway inflammation is a critical feature of lower respiratory tract infections caused by viruses such as respiratory syncytial virus (RSV). A growing body of literature has demonstrated the importance of extracellular matrix changes such as the accumulation of hyaluronan (HA) and versican in the subepithelial space in promoting airway inflammation; however, whether these factors contribute to airway inflammation during RSV infection remains unknown. To test the hypothesis that RSV infection promotes inflammation via altered HA and versican production, we studied an ex vivo human bronchial epithelial cell (BEC)/human lung fibroblast (HLF) coculture model. RSV infection of BEC/HLF cocultures led to decreased hyaluronidase expression by HLFs, increased accumulation of HA, and enhanced adhesion of U937 cells as would be expected with increased HA. HLF production of versican was not altered following RSV infection; however, BEC production of versican was significantly downregulated following RSV infection. In vivo studies with epithelial-specific versican-deficient mice [SPC-Cre(+) Vcan] demonstrated that RSV infection led to increased HA accumulation compared with control mice, which also coincided with decreased hyaluronidase expression in the lung. SPC-Cre(+) Vcan mice demonstrated enhanced recruitment of monocytes and neutrophils in bronchoalveolar lavage fluid and increased neutrophils in the lung compared with SPC-Cre(-) RSV-infected littermates. Taken together, these data demonstrate that altered extracellular matrix accumulation of HA occurs following RSV infection and may contribute to airway inflammation. In addition, loss of epithelial expression of versican promotes airway inflammation during RSV infection further demonstrating that versican's role in inflammatory regulation is complex and dependent on the microenvironment.
Topics: Animals; Bronchoalveolar Lavage Fluid; Coculture Techniques; Epithelial Cells; Humans; Hyaluronan Synthases; Hyaluronic Acid; Hyaluronoglucosaminidase; Lung; Mice; Respiratory Syncytial Virus Infections; U937 Cells; Versicans
PubMed: 33187989
DOI: 10.1074/jbc.RA120.016196 -
Biomedicines Apr 2022Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair...
Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair loss must be developed, and electromagnetic field (EMF) therapy has been proven to be a promising medical treatment in various fields, including hair loss treatment. This study evaluated the effect of extremely low-frequency electromagnetic field (ELF-EMF) intensity and exposure time by analyzing the expression of cytokines and anagen-related molecules, which influence hair activation and growth, in hair bulb spheroid (HBS) and hair follicle (HF) organ cultures. ELF-EMFs did not induce toxicity in the HBSs, as verified via the lactate dehydrogenase (LDH) assay. Moreover, an ELF-EMF intensity of 5-20 G promoted the expression of ALP, versican, β-catenin, and several cytokines (VEGF, PDGF, FGF-10, and ET-1) in HBSs. Immunohistochemical staining showed that ELF-EMF at an intensity of 5-20 G upregulated ALP and β-catenin and decreased TUNEL staining in HBS. Moreover, HFs exposed to ELF-EMF for 60 min exhibited an increase in hair length and a 1.5-fold increase in IL-4, ICAM-1, ALP, and versican mRNA expression compared to the control. Immunohistochemical staining indicated that 60 min of ELF-EMF can increase the expression of ALP and β-catenin and decreases TUNEL staining in organ cultures. Collectively, our results demonstrated that ELF-EMF exposure at a 10 G intensity for 60 min promoted hair shaft growth in HFs due to the effect of cytokines and adhesion molecules via the Wnt/β-catenin pathway. Therefore, ELF-EMF is a promising treatment for hair loss.
PubMed: 35453674
DOI: 10.3390/biomedicines10040924