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American Journal of Translational... 2023Versican (VCAN), a member of the multifunctional glycoprotein family, is involved in various aspects of cancer progression. However, the role of VCAN in diverse cancers...
OBJECTIVE
Versican (VCAN), a member of the multifunctional glycoprotein family, is involved in various aspects of cancer progression. However, the role of VCAN in diverse cancers remains poorly defined. This research aimed to investigate the correlation between VCAN expression and the oncogenic role, as well as visualize its prognostic landscape in pan-cancer.
METHODS
Raw data in regard to VCAN expression in cancer patients were acquired from GEO GeneChip public database in NCBI. Besides, we selected microarray data GSE16088 for analysis. We retrieved the genes associated with osteosarcoma (OS) from the OMIM database and identified their intersection with the core module. VCAN was suggested to be a potential marker gene for OS. Subsequently, we conducted Gene Set Enrichment Analysis (GSEA) to explore gene functional enrichment. Moreover, we performed pan-cancer analysis on VCAN to gain a comprehensive understanding of its implications across various cancer types.
RESULTS
The VCAN expression in the tumor tissue was higher than that in normal tissue. Elevated expression of VCAN was associated with high the tumor stage and poor long-term survival. There was a significant positive correlation between VCAN and cancer fibroblasts in all pan cancers. Moreover, FBN1 was the intersection gene of VCAN-related genes and linker genes. ANTXR1, COL5A2, CSGALNACT2, and SPARC were the target genes of VCAN genes. GSEA analysis showed that VCAN was mainly enriched in the extracellular matrix (ECM) signaling pathway.
CONCLUSION
VCAN can be used as a marker molecule for the early diagnosis of OS and holds significance as a molecule in cases of OS with distant metastasis. The ECM signaling pathway may be a core pathway in OS development and distant metastasis. These findings shed new light on therapeutics of cancers.
PubMed: 37854213
DOI: No ID Found -
The Turkish Journal of Pediatrics 2024Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the...
BACKGROUND
Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the fifth finger (camptodactyly); noninflammatory arthropathy; decreased angle between the shaft and the head of the femur (coxa vara) and pericarditis. Its association with mitral stenosis has not yet been reported. Hereby we report this unique association with CACP syndrome.
CASE
An eleven-year-old girl presented with non-productive cough, dyspnea, and orthopnea. She was diagnosed CACP syndrome at the age of seven and a biallelic frameshift mutation in the PRG4 gene was determined. The physical examination revealed pectus excavatum, camptodactyly, genu valgum, tachypnea and orthopnea. The functional capacity was NYHA III-IV. She had 2/6 soft pansystolic murmur at 4th left intercostal space and a rumbling diastolic murmur at apex. Echocardiography revealed an enlarged left atrium, severe stenotic mitral valve with a mean diastolic transmitral gradient of 22.5 mmHg, mild mitral regurgitation and mild apical pericardial effusion. The patient had mitral comissurotomy and partial pericardiectomy operation. Her post-operative transmitral gradient decreased to 6.9 mmHg and the pulmonary pressure was 30 mmHg. Her functional capacity increased to NYHA I-II.
CONCLUSIONS
The main defect is the proteoglycan 4 protein which acts like a lubricant in articular and visceral surfaces. Therefore, the leading clinical feature is arthropathy. Cardiac involvement other than clinically mild pericarditis is not usually expected. Three types of proteoglycans (decorin, biglycan, and versican) are present in the mitral valve. This could be the reason of mitral valve involvement in rare cases as like ours. It is important that these patients undergo echocardiographic examination regularly.
Topics: Female; Humans; Child; Coxa Vara; Mitral Valve Stenosis; Joint Diseases; Pericarditis; Dyspnea; Arthropathy, Neurogenic; Hand Deformities, Congenital; Synovitis
PubMed: 38523390
DOI: 10.24953/turkjped.2023.647 -
Frontiers in Neuroanatomy 2024Normal brain development requires continuous communication between developing neurons and their environment filled by a complex network referred to as extracellular...
Normal brain development requires continuous communication between developing neurons and their environment filled by a complex network referred to as extracellular matrix (ECM). The ECM is divided into distinct families of molecules including hyaluronic acid, proteoglycans, glycoproteins such as tenascins, and link proteins. In this study, we characterize the temporal and spatial distribution of the extracellular matrix molecules in the embryonic and postnatal mouse hindbrain by using antibodies and lectin histochemistry. In the embryo, hyaluronan and neurocan were found in high amounts until the time of birth whereas versican and tenascin-R were detected in lower intensities during the whole embryonic period. After birth, both hyaluronic acid and neurocan still produced intense staining in almost all areas of the hindbrain, while tenascin-R labeling showed a continuous increase during postnatal development. The reaction with WFA and aggrecan was revealed first 4th postnatal day (P4) with low staining intensities, while HAPLN was detected two weeks after birth (P14). The perineuronal net appeared first around the facial and vestibular neurons at P4 with hyaluronic acid cytochemistry. One week after birth aggrecan, neurocan, tenascin-R, and WFA were also accumulated around the neurons located in several hindbrain nuclei, but HAPLN1 was detected on the second postnatal week. Our results provide further evidence that many extracellular macromolecules that will be incorporated into the perineuronal net are already expressed at embryonic and early postnatal stages of development to control differentiation, migration, and synaptogenesis of neurons. In late postnatal period, the experience-driven neuronal activity induces formation of perineuronal net to stabilize synaptic connections.
PubMed: 38496826
DOI: 10.3389/fnana.2024.1369103 -
BMC Pulmonary Medicine Apr 2024The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in...
BACKGROUND
The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis.
METHODS
Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay.
RESULTS
The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001).
CONCLUSIONS
Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis.
Topics: Humans; Bronchiectasis; Male; Female; Middle Aged; Retrospective Studies; Versicans; Adult; Pseudomonas aeruginosa; Epithelial Cells; Aged; Up-Regulation; Coculture Techniques; Bronchi; Cell Line; RNA, Messenger; Case-Control Studies; Clinical Relevance
PubMed: 38685004
DOI: 10.1186/s12890-024-03027-4 -
Cell Proliferation Jan 2024Cellular spheroids have been described as an appropriate culture system to restore human follicle dermal papilla cells (hFDPc) intrinsic properties; however, they show a...
Cellular spheroids have been described as an appropriate culture system to restore human follicle dermal papilla cells (hFDPc) intrinsic properties; however, they show a low and variable efficiency to promote complete hair follicle formation in in vivo experiments. In this work, a conscientious analysis revealed a 25% cell viability in the surface of the dermal papilla spheroid (DPS) for all culture conditions, questioning whether it is an appropriate culture system for hFDPc. To overcome this problem, we propose the use of human blood plasma for the generation of fibrin microgels (FM) with encapsulated hFDPc to restore its inductive signature, either in the presence or in the absence of blood platelets. FM showed a morphology and extracellular matrix composition similar to the native dermal papilla, including Versican and Collagen IV and increasing cell viability up to 85%. While both systems induce epidermal invaginations expressing hair-specific keratins K14, K15, K71, and K75 in in vitro skin cultures, the number of generated structures increases from 17% to 49% when DPS and FM were used, respectively. These data show the potential of our experimental setting for in vitro hair follicle neogenesis with wild adult hFDPc using FM, being a crucial step in the pursuit of human hair follicle regeneration therapies.
Topics: Humans; Hair Follicle; Microgels; Fibrin; Skin; Epidermis; Cells, Cultured
PubMed: 37539497
DOI: 10.1111/cpr.13528 -
Communications Biology Mar 2024Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal...
Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.
Topics: Female; Humans; Infant, Newborn; Pregnancy; ADAMTS4 Protein; Amnion; Inflammation; Parturition; Peptide Hydrolases; Premature Birth; Versicans; Animals; Mice
PubMed: 38461223
DOI: 10.1038/s42003-024-06007-w -
Cell Reports May 2024Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we...
Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory.
Topics: Animals; Extracellular Matrix; Long-Term Potentiation; Mice; Neuronal Plasticity; Memory; Synapses; Mice, Inbred C57BL; Male; CA1 Region, Hippocampal; Hippocampus
PubMed: 38676925
DOI: 10.1016/j.celrep.2024.114112 -
Biomedical Reports Jan 2024Chemotherapy with temozolomide (TMZ) is an essential part of anticancer therapy used for malignant tumors (mainly melanoma and glioblastoma); however, the long-term...
Chemotherapy with temozolomide (TMZ) is an essential part of anticancer therapy used for malignant tumors (mainly melanoma and glioblastoma); however, the long-term effects on patient health and life quality are not fully investigated. Considering that tumors often occur in elderly patients, the present study was conducted on long-term (4 months) treatment of adult Wistar rats (9 months old, n=40) with TMZ and/or dexamethasone (DXM) to investigate potential behavioral impairments or morphological and molecular changes in their brain tissues. According to the elevated plus maze test, long-term use of TMZ affected the anxiety of the adult Wistar rats, although no significant deterioration of brain morphology or cellular composition of the brain tissue was revealed. The expression levels of all studied heparan sulfate (HS) proteoglycans (HSPGs) (syndecan-1, syndecan-3, glypican-1 and HSPG2) and the majority of the studied chondroitin sulfate (CS) proteoglycans (CSPGs) (decorin, biglycan, lumican, brevican, neurocan aggrecan, versican, Cspg4/Ng2, Cspg5 and phosphacan) were not affected by TMZ/DXM, except for neurocan and aggrecan. Aggrecan was the most sensitive proteoglycan to TMZ/DXM treatment demonstrating downregulation of its mRNA and protein levels following TMZ (-10-fold), DXM (-45-fold) and TMZ-DXM (-80-fold) treatment. HS content was not affected by TMZ/DXM treatment, whereas CS content was decreased 1.5-2.5-fold in the TMZ- and DXM-treated brain tissues. Taken together, the results demonstrated that treatment of adult Wistar rats with TMZ had long-term effects on the brain tissues, such as decreased aggrecan core protein levels and CS chain content and increased anxiety of the experimental animals.
PubMed: 38124768
DOI: 10.3892/br.2023.1695 -
Experimental and Therapeutic Medicine Jan 2024[This retracts the article DOI: 10.3892/etm.2014.1708.].
[This retracts the article DOI: 10.3892/etm.2014.1708.].
PubMed: 38125350
DOI: 10.3892/etm.2023.12308 -
Experimental and Therapeutic Medicine Feb 2024[This retracts the article DOI: 10.3892/etm.2017.4998.].
[This retracts the article DOI: 10.3892/etm.2017.4998.].
PubMed: 38234615
DOI: 10.3892/etm.2023.12346