scholarly journals The Extracellular Matrix Glycoprotein Tenascin C and Adult Neurogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Milena Tucić ◽  
Vera Stamenković ◽  
Pavle Andjus
Keyword(s):  
Extracellular Matrix ◽  
Adult Neurogenesis ◽  
Specific Reference ◽  
Neuron Development ◽  
Regulatory Pathways ◽  
Tenascin C ◽  
Extracellular Matrix Components ◽  
Adult Hippocampus ◽  
And Migration ◽  
Regenerative Therapies

Tenascin C (TnC) is a glycoprotein highly expressed in the extracellular matrix (ECM) during development and in the adult central nervous system (CNS) in regions of active neurogenesis, where neuron development is a tightly regulated process orchestrated by extracellular matrix components. In addition, newborn cells also communicate with glial cells, astrocytes and microglia, indicating the importance of signal integration in adult neurogenesis. Although TnC has been recognized as an important molecule in the regulation of cell proliferation and migration, complete regulatory pathways still need to be elucidated. In this review we discuss the formation of new neurons in the adult hippocampus and the olfactory system with specific reference to TnC and its regulating functions in this process. Better understanding of the ECM signaling in the niche of the CNS will have significant implications for regenerative therapies.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

Regulation of mesenchymal extracellular matrix protein synthesis by transforming growth factor-beta and glucocorticoids in tumor stroma

1995 ◽  
Vol 108 (6) ◽  
pp. 2153-2162 ◽  
Author(s):  
J.F. Talts ◽  
A. Weller ◽  
R. Timpl ◽  
M. Ekblom ◽  
P. Ekblom
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tenascin C ◽  
Extracellular Matrix Components ◽  
Growth Factor Beta ◽  
Matrix Components

We have here studied the composition and regulation of stromal extracellular matrix components in an experimental tumor model. Nude mice were inoculated with WCCS-1 cells, a human Wilms' tumor cell line. In the formed tumors the stroma was found to contain mesenchymal extracellular matrix proteins such as tenascin-C, fibulins-1 and 2 and fibronectin, but no nidogen. Nidogen was confined to basement membranes of tumor blood vessels. Since glucocorticoids have been shown to downregulate tenascin-C expression in vitro, we tested whether dexamethasone can influence biosynthesis of extracellular matrix components during tumor formation in vivo. A downregulation of tenascin-C mRNA and an upregulation of fibronectin mRNA expression by dexamethasone was noted. Transforming growth factor-beta 1 mRNA levels were unaffected by the dexamethasone treatment. Glucocorticoids can thus downregulate tenascin-C synthesis although local stimulatory growth factors are present. The competition between a negative and a positive extrinsic factor on synthesis of stromal extracellular matrix components was studied in a fibroblast/preadipocyte cell line. Transforming growth factor-beta 1 stimulated tenascin-C synthesis but did not affect fibronectin or fibulin-2 synthesis. Dexamethasone at high concentrations could completely suppress the effect of transforming growth factor-beta 1 on tenascin-C mRNA expression. Transforming growth factor-beta 1 could in turn overcome the downregulation of tenascin-C mRNA expression caused by a lower concentration of dexamethasone. We therefore suggest that the limited expression of tenascin-C in part is due to a continuous suppression by physiological levels of glucocorticoids, which can be overcome by local stimulatory growth factors when present in sufficient amounts.

scholarly journals Adaption of Lung Fibroblasts to Fluoro-Edenite Fibers: Evaluation of Molecular and Physiological Dynamics

2021 ◽  
Vol 55 (3) ◽  
pp. 327-343
Keyword(s):  
Extracellular Matrix ◽  
Environmental Pollutant ◽  
Lung Fibroblasts ◽  
Public Health Issue ◽  
Mitochondrial Activity ◽  
Cell Growth And Migration ◽  
Senescent Phenotype ◽  
Extracellular Matrix Components ◽  
And Migration

Background/Aims: The fluoro-edenite fibrous amphibole was identified as an environmental pollutant associate to risk of carcinogenicity. In Sicily (Italy), it represents a public health issue because fluoro-edenite fibers are present in the soil of Biancavilla, a town located on the south-west slopes of the volcano Etna. Since the relationship between exposure to fluoro-edenite and the onset of lung disorders have been documented, in vitro studies were performed to clarify the mechanisms of damage, but most aspects remain unknown. Here, we focus on the effects of mineral fibers in a primary culture of lung fibroblasts. We supposed that the cells react to fluoro-edenite exposure by establishing a process of adaption that could modify their metabolic activity, their proliferation, and their physiological functions, as the production of extracellular matrix (ECM) components. Methods: To verify our hypothesis, we used immunofluorescence, cell proliferation, senescence, apoptosis, scratch, Western blot, Reverse transcription-polymerase chain reaction (RT-PCR), and evaluation of extracellular matrix components assays. Results: Results demonstrated that lung fibroblasts react to fluoro-edenite by a down-regulation of mitochondrial activity, a reduction of cell growth and migration, and a resistance to apoptosis. These elements suggested the induction of a premature senescent phenotype that was confirmed by senescence-associated beta-galactosidase (SA-β-Gal) activity, and by the analysis of ECM elements. We found an unbalance of collagens ratio, and changes in matrix metalloproteinase3 production and release. Conclusion: Our data suggest that fluoro-edenite-induced senescence of lung fibroblasts could be an early and underestimated step that may drive fibroblasts toward a fibrotic and carcinogenic phenotype.

Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration

Development ◽  
2001 ◽  
Vol 128 (13) ◽  
pp. 2485-2496 ◽  
Author(s):  
Emmanuel Garcion ◽  
Andreas Faissner ◽  
Charles ffrench-Constant
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Knockout Mice ◽  
Neural Precursor ◽  
Αvβ3 Integrin ◽  
Tenascin C ◽  
Oligodendrocyte Precursor ◽  
And Migration ◽  
Proliferation And Migration

The extracellular matrix glycoprotein tenascin-C is widely expressed in the vertebrate central nervous system (CNS) during development and repair. Despite multiple effects of tenascin-C on cell behaviour in culture, no structural abnormalities of the CNS and other organs have been found in adult tenascin-C-null mice, raising the question of whether this glycoprotein has a significant role in vivo. Using a transgenic approach, we have demonstrated that tenascin-C regulates both cell proliferation and migration in oligodendrocyte precursors during development. Knockout mice show increased rates of oligodendrocyte precursor migration along the optic nerve and reduced rates of oligodendrocyte precursor proliferation in different regions of the CNS. Levels of programmed cell death were reduced in areas of myelination at later developmental stages,providing a potential corrective mechanism for any reduction in cell numbers that resulted from the proliferation phenotype. The effects on cell proliferation are mediated via the αvβ3 integrin and an interaction with the platelet-derived growth factor-stimulated mitogenic pathway, emphasising the importance of both CNS extracellular matrix and integrin growth factor interactions in the regulation of neural precursor behaviour.

Changes in the distribution of extracellular matrix components during neural crest development in Xiphophorus spp. embryos

1994 ◽  
Vol 72 (7) ◽  
pp. 1340-1353 ◽  
Author(s):  
Bahram Sadaghiani ◽  
Bruce J. Crawford ◽  
Juergen R. Vielkind
Keyword(s):  
Extracellular Matrix ◽  
Neural Crest ◽  
Critical Role ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Weak Staining ◽  
Extracellular Matrix Components ◽  
Neural Crest Cell Migration ◽  
And Migration ◽  
Migration Pathways

The changes in distribution of chondroitin sulfate proteoglycans (CSs) and fibronectin (FN), two major components of the extracellular matrix (ECM), are described during the development and migration of neural crest cells in two Xiphophorus species offish, X. helleri (swordtail) and X. maculatus (platyfish), using immunohistochemistry. A detailed description of the developmental changes in HNK-1-positive ECM components is also provided and compared with those of CSs and FN. HNK-1 antigen was also used as a marker for the neural crest cells. Weak staining for CSs, FN, and HNK-1-positive ECM was present in the neural crest cell migration pathways prior to migration of the cells. The level of staining increased dramatically during migration of these cells and decreased again after migration was nearly completed. Staining for CSs was more widespread than staining for FN, while the HNK-1 staining pattern was more clearly restricted to the migratory pathways than those seen with the other two antibodies. The correlation between the spatiotemporal relationship of these ECM components and the segregation and migration of neural crest cells suggests that these ECM molecules may be involved in both initiating and guiding the migration of neural crest cells in these fish. The HNK-1-positive ECM may play a more critical role than CSs and FN.

scholarly journals Extracellular Matrix Remodeling in the Retina and Optic Nerve of a Novel Glaucoma Mouse Model

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 169
Author(s):  
Jacqueline Reinhard ◽  
Susanne Wiemann ◽  
Sebastian Hildebrandt ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Optic Nerve ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Nerve Fibers ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Protein Tyrosine ◽  
Tenascin C ◽  
Iop Elevation

Glaucoma is a neurodegenerative disease that is characterized by the loss of retinal ganglion cells (RGC) and optic nerve fibers. Increased age and intraocular pressure (IOP) elevation are the main risk factors for developing glaucoma. Mice that are heterozygous (HET) for the mega-karyocyte protein tyrosine phosphatase 2 (PTP-Meg2) show chronic and progressive IOP elevation, severe RGCs loss, and optic nerve damage, and represent a valuable model for IOP-dependent primary open-angle glaucoma (POAG). Previously, evidence accumulated suggesting that glaucomatous neurodegeneration is associated with the extensive remodeling of extracellular matrix (ECM) molecules. Unfortunately, little is known about the exact ECM changes in the glaucomatous retina and optic nerve. Hence, the goal of the present study was to comparatively explore ECM alterations in glaucomatous PTP-Meg2 HET and control wild type (WT) mice. Due to their potential relevance in glaucomatous neurodegeneration, we specifically analyzed the expression pattern of the ECM glycoproteins fibronectin, laminin, tenascin-C, and tenascin-R as well as the proteoglycans aggrecan, brevican, and members of the receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) family. The analyses were carried out in the retina and optic nerve of glaucomatous PTP-Meg2 HET and WT mice using quantitative real-time PCR (RT-qPCR), immunohistochemistry, and Western blot. Interestingly, we observed increased fibronectin and laminin levels in the glaucomatous HET retina and optic nerve compared to the WT group. RT-qPCR analyses of the laminins α4, β2 and γ3 showed an altered isoform-specific regulation in the HET retina and optic nerve. In addition, an upregulation of tenascin-C and its interaction partner RPTPβ/ζ/phosphacan was found in glaucomatous tissue. However, comparable protein and mRNA levels for tenascin-R as well as aggrecan and brevican were observed in both groups. Overall, our study showed a remodeling of various ECM components in the glaucomatous retina and optic nerve of PTP-Meg2 HET mice. This dysregulation could be responsible for pathological processes such as neovascularization, inflammation, and reactive gliosis in glaucomatous neurodegeneration.

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