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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 -
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 -
Vestnik Oftalmologii 2024Degenerative changes in the peripheral regions of the ocular fundus allow a closer look at both the role of collagen genes and their mutations in children with high...
UNLABELLED
Degenerative changes in the peripheral regions of the ocular fundus allow a closer look at both the role of collagen genes and their mutations in children with high myopia.
PURPOSE
The study investigates the features of genetic mutations in children with high myopia combined with peripheral retinal degenerations.
MATERIAL AND METHODS
Study group was formed from the database of genetic studies of the Scientific and Clinical Center OOO Oftalmic, which consists of 4362 patients referred for medical genetic counseling and molecular genetic testing from 2016 to 2021. Selection criteria were: male and female patients, aged 5-18 years old, who had the following clinical signs: high myopia (>6.00 D) and the presence of peripheral retinal degenerations (PRD). The study considered both isolated cases of ophthalmic pathology, as well as its syndromic forms. The final selection included 40 children. All patients had consulted with a geneticist. Whole-exome sequencing (WES), next generation sequencing (NGS), and single gene sequencing were conducted by taking 5 mL of peripheral venous blood and extracting deoxyribonucleic acid (DNA).
RESULTS
In patients with isolated cases of ophthalmic pathology (peripheral retinal degenerations and high myopia) with a confirmed genetic diagnosis, mutations in the gene were detected in 77.4% of cases, and in the gene - in 22.6% of cases. In Stickler syndrome with a confirmed genetic diagnosis, mutations in the gene were detected in 33.3% of cases. In Marshall syndrome, the mutation in the gene was detected in 11.1% of cases. In children with Ehlers-Danlos, Knobloch type 1, Cohen, Marfan, Wagner syndromes mutations in the genes , , , , were detected in 55.6% of cases. In 33.3% of cases of Knobloch type 1, Cohen, Wagner syndromes the mutation is found in both copies of the gene (i.e., in both chromosomes), which leads to the development of peripheral retinal degenerations with high myopia.
CONCLUSION
The results of the conducted molecular genetic testing expand our understanding of the mutation spectrum in the genes of children with both isolated cases of ophthalmic pathology, as well as syndromic pathology.
Topics: Child; Humans; Female; Male; Child, Preschool; Adolescent; Retinal Degeneration; Mutation; Eye Diseases, Hereditary; Arthritis; Versicans
PubMed: 38450462
DOI: 10.17116/oftalma202414001119 -
Journal of Biomedical Materials... Jul 2024Extracellular matrix-based bio-scaffolds are useful for tissue engineering as they retain the unique structural, mechanical, and physiological microenvironment of the...
Extracellular matrix-based bio-scaffolds are useful for tissue engineering as they retain the unique structural, mechanical, and physiological microenvironment of the tissue thus facilitating cellular attachment and matrix activities. However, considering its potential, a comprehensive understanding of the protein profile remains elusive. Herein, we evaluate the impact of decellularization on the human amniotic membrane (hAM) based on its proteome profile, physicochemical features, as well as the attachment, viability, and proliferation of umbilical cord-derived mesenchymal stem cells (hUC-MSC). Proteome profiles of decellularized hAM (D-hAM) were compared with hAM, and gene ontology (GO) enrichment analysis was performed. Proteomic data revealed that D-hAM retained a total of 249 proteins, predominantly comprised of extracellular matrix proteins including collagens (collagen I, collagen IV, collagen VI, collagen VII, and collagen XII), proteoglycans (biglycan, decorin, lumican, mimecan, and versican), glycoproteins (dermatopontin, fibrinogen, fibrillin, laminin, and vitronectin), and growth factors including transforming growth factor beta (TGF-β) and fibroblast growth factor (FGF) while eliminated most of the intracellular proteins. Scanning electron microscopy was used to analyze the epithelial and basal surfaces of D-hAM. The D-hAM displayed variability in fibril morphology and porosity as compared with hAM, showing loosely packed collagen fibers and prominent large pore areas on the basal side of D-hAM. Both sides of D-hAM supported the growth and proliferation of hUC-MSC. Comparative investigations, however, demonstrated that the basal side of D-hAM displayed higher hUC-MSC proliferation than the epithelial side. These findings highlight the importance of understanding the micro-environmental differences between the two sides of D-hAM while optimizing cell-based therapeutic applications.
Topics: Humans; Mesenchymal Stem Cells; Amnion; Umbilical Cord; Proteome; Cell Proliferation; Decellularized Extracellular Matrix; Biocompatible Materials
PubMed: 38380793
DOI: 10.1002/jbm.a.37685 -
Molecular Neurobiology Feb 2024Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed...
Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed photobiomodulation (PBM) could effectively downregulate the process of inflammation with modification of macrophage polarization after SCI; however, the potential mechanism behind that is still unclear. In the presented study, we aimed to investigate the effect of PBM on the expression level of versican, a matrix molecular believed to be associated with inflammation, and tried to find the mechanism on how that could regulate the inflammation process. Using immunofluorescence technique and western blot, we found the expression level of versican is increased after injury and markedly downregulated by irradiation treatment. Using virus intrathecal injection, we found the knock-down of versican could produce the effect similar to that of PBM and might have an effect on inflammation and macrophage polarization after SCI. To further verify the deduction, we peptide the supernatant of astrocytes to induce M0, M1, and M2 macrophages. We found that the versican produced by astrocytes might have a role on the promotion of M2 macrophages to inflammatory polarization. Finally, we investigated the potential pathway in the regulation of M2 polarization with the induction of versican. This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI.
PubMed: 38363534
DOI: 10.1007/s12035-024-03980-5 -
Chinese Journal of Traumatology =... Mar 2024Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury.... (Review)
Review
PURPOSE
Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.
METHODS
Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.
RESULTS
Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI.
CONCLUSION
This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.
Topics: Humans; Biomarkers; Protein Interaction Maps; Prognosis; Gene Expression Profiling; Acute Kidney Injury; Computational Biology
PubMed: 38296680
DOI: 10.1016/j.cjtee.2024.01.002 -
Matrix Biology Plus Feb 2024Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque...
Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.
PubMed: 38292008
DOI: 10.1016/j.mbplus.2024.100141 -
Cell Death & Disease Jan 2024The global burden of colorectal cancer (CRC) has rapidly increased in recent years. Dysregulated cholesterol homeostasis facilitated by extracellular matrix (ECM)...
The global burden of colorectal cancer (CRC) has rapidly increased in recent years. Dysregulated cholesterol homeostasis facilitated by extracellular matrix (ECM) remodeling transforms the tumor microenvironment. Collagen I, a major with ECM component is highly expressed in colorectal tumors with infiltrative growth. Although oxysterol binding protein (OSBP)-related proteins accommodate tumorigenesis, OSBPL2, which is usually involved in deafness, is not associated with CRC progression. Therefore, we aimed to investigate the pathological function of OSBPL2 and identify the molecular link between ECM-Collagen I and OSBPL2 in CRC to facilitate the development of new treatments for CRC. OSBPL2 predicted a favorable prognosis in stage IV CRC and substantially repressed Collagen I-induced focal adhesion, migration, and invasion. The reduction of OSBPL2 activated ERK signaling through the VCAN/AREG/EREG axis during CRC growth, while relying on PARP1 via ZEB1 in CRC metastasis. OSBPL2 defect supported colorectal tumor growth and metastasis, which were suppressed by the ERK and PARP1 inhibitors SCH772984 and AG14361, respectively. Overall, our findings revealed that the Collagen I-induced loss of OSBPL2 aggravates CRC progression through VCAN-mediated ERK signaling and the PARP1/ZEB1 axis. This demonstrates that SCH772984 and AG14361 are reciprocally connective therapies for OSBPL2 CRC, which could contribute to further development of targeted CRC treatment.
Topics: Humans; Benzodiazepines; Azulenes; Collagen Type I; Colorectal Neoplasms; Tumor Microenvironment; Zinc Finger E-box-Binding Homeobox 1; Receptors, Steroid; Versicans; Poly (ADP-Ribose) Polymerase-1
PubMed: 38267463
DOI: 10.1038/s41419-024-06468-1 -
Fukushima Journal of Medical Science Jan 2024Extracellular matrix (ECM) is a non-cellular constituent found in all tissues and organs. Although ECM was previously recognized as a mere "molecular glue" that supports... (Review)
Review
Extracellular matrix (ECM) is a non-cellular constituent found in all tissues and organs. Although ECM was previously recognized as a mere "molecular glue" that supports the tissue structure of organs such as the lungs, it has recently been reported that ECM has important biological activities for tissue morphogenesis, inflammation, wound healing, and tumor progression. Proteoglycans are the main constituent of ECM, with growing evidence that proteoglycans and their associated glycosaminoglycans play important roles in the pathogenesis of several diseases. However, their roles in the lungs are incompletely understood. Leukocyte migration into the lung is one of the main aspects involved in the pathogenesis of several lung diseases. Glycosaminoglycans bind to chemokines and their interaction fine-tunes leukocyte migration into the affected organs. This review focuses on the role chemokine and glycosaminoglycan interactions in neutrophil migration into the lung. Furthermore, this review presents the role of proteoglycans such as syndecan, versican, and hyaluronan in inflammatory and fibrotic lung diseases.
Topics: Humans; Lung; Extracellular Matrix; Glycosaminoglycans; Versicans; Lung Diseases
PubMed: 38267030
DOI: 10.5387/fms.2023-07 -
International Journal of Molecular... Jan 2024Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and...
Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced ( < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen ( < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.
Topics: Humans; Biglycan; Decorin; Atherosclerosis; Plaque, Atherosclerotic; Extracellular Matrix Proteins; Aspirin; Collagen Type I; Thrombosis
PubMed: 38256024
DOI: 10.3390/ijms25020950