scholarly journals The role of extracellular matrix in mouse and human corneal neovascularization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
M. Barbariga ◽  
F. Vallone ◽  
E. Mosca ◽  
F. Bignami ◽  
C. Magagnotti ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Medical Condition ◽  
Corneal Stroma ◽  
Acanthamoeba Keratitis ◽  
Corneal Neovascularization ◽  
Collagen Vi ◽  
Tenascin C ◽  
Human Proteins ◽  
Specific Proteins

Abstract Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularized vs healthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.

The extracellular matrix of the developing cornea: diversity, deposition and function*

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 195-205
Author(s):  
J. B. L. Bard ◽  
M. K. Bansal ◽  
A. S. A. Ross
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulphate ◽  
Corneal Stroma ◽  
Experimental System ◽  
Collagen I ◽  
And Function ◽  
20 Nm

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differentiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morphogenesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen I. We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a result implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere. The latter part of the paper describes our current work on chick stromal deposition using corneal epithelia isolated with an intact basal lamina that lay down in vitro ∼3μm-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epithelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more autonomous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibrildiameter distribution are indistinguishable from controls. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deforming their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.

scholarly journals Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 409 ◽  
Author(s):  
Manuela Antoniel ◽  
Francesco Traina ◽  
Luciano Merlini ◽  
Davide Andrenacci ◽  
Domenico Tigani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Critical Role ◽  
Active Form ◽  
Congenital Muscular Dystrophy ◽  
Cell Polarization ◽  
Pcr Analysis ◽  
Matrix Remodeling ◽  
Collagen Vi

Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.

Electrostatic Contribution of the Proteoglycans to the In-Plane Shear and Compressive Stiffness of Corneal Stroma

2010 ◽  
Author(s):  
Hamed Hatami-Marbini ◽  
Peter M. Pinsky
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Electrostatic Interactions ◽  
Corneal Stroma ◽  
Collagen Fibers ◽  
Connective Tissues ◽  
Compressive Stiffness ◽  
Electrostatic Contribution ◽  
Repulsive Forces

The extracellular matrix (ECM) is a fibrous structure embedded in an aqueous gel. The mechanical and electrostatic interactions of the ECM constituents, i.e. collagen fibers and proteoglycans (PGs), define the structure and mechanical response of connective tissues (CTs) such as cornea and articular cartilage. Proteoglycans are complex macromolecules consisting of linear chains of repeating gylcosaminoglycans (GAGs) which are covalently attached to a core protein. PGs can be as simple as decorin with a single GAG side chain or as complex as aggrecan with many GAGs. Decorin is the simplest small leucine-rich PG and is the main PG inside the corneal stroma. It has an arch shape and links non-covalently at its concave surface to the collagen fibrils. It has been shown that while collagen fibers inside the extracellular matrix resist the tensile forces, the negatively charged glycosaminoglycans and their interaction with water give compressive stiffness to the tissue. The role of PGs in biomechanical properties of the connective tissues has mainly been studied in order to explore the behavior of articular cartilage [1], which is a CT with large and highly negatively charged PGs, aggrecans. In order to explain the role of PGs in this tissue, it is commonly assumed that their contribution to the CT elasticity is because of both the repulsive forces between negatively charged GAGs and GAG interactions with free mobile charges in the ionic bath. The electrostatic contribution to the shear and compressive stiffness of cartilage is modeled by approximating GAGs as charged rods [1]. The Poisson-Boltzmann equation is used to compute the change in electrical potential and mobile ion distributions which are caused by the macroscopic deformation.

Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation

2019 ◽  
Vol 47 (6) ◽  
pp. 1651-1660 ◽  
Author(s):  
Susanne Wiemann ◽  
Jacqueline Reinhard ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Intracellular Signaling ◽  
Matrix Protein ◽  
Dynamic Network ◽  
Adaptor Proteins ◽  
Extracellular Matrix Protein ◽  
Tenascin C ◽  
Pathological Conditions ◽  
Main Components

The extracellular matrix (ECM) consists of a dynamic network of various macromolecules that are synthesized and released by surrounding cells into the intercellular space. Glycoproteins, proteoglycans and fibrillar proteins are main components of the ECM. In addition to general functions such as structure and stability, the ECM controls several cellular signaling pathways. In this context, ECM molecules have a profound influence on intracellular signaling as receptor-, adhesion- and adaptor-proteins. Due to its various functions, the ECM is essential in the healthy organism, but also under pathological conditions. ECM constituents are part of the glial scar, which is formed in several neurodegenerative diseases that are accompanied by the activation and infiltration of glia as well as immune cells. Remodeling of the ECM modulates the release of pro- and anti-inflammatory cytokines affecting the fate of immune, glial and neuronal cells. Tenascin-C is an ECM glycoprotein that is expressed during embryonic central nervous system (CNS) development. In adults it is present at lower levels but reappears under pathological conditions such as in brain tumors, following injury and in neurodegenerative disorders and is highly associated with glial reactivity as well as scar formation. As a key modulator of the immune response during neurodegeneration in the CNS, tenascin-C is highlighted in this mini-review.

scholarly journals Extracellular Matrix of Glioblastoma Inhibits Polarization and Transmigration of T Cells: The Role of Tenascin-C in Immune Suppression

2010 ◽  
Vol 185 (3) ◽  
pp. 1450-1459 ◽  
Author(s):  
Jyun-Yuan Huang ◽  
Yu-Jung Cheng ◽  
Yu-Ping Lin ◽  
Huan-Ching Lin ◽  
Chung-Chen Su ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Immune Suppression ◽  
Tenascin C

scholarly journals Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5

2020 ◽  
Vol 9 (4) ◽  
pp. 991 ◽  
Author(s):  
Elizabeth Brett ◽  
Matthias Sauter ◽  
Éadaoin Timmins ◽  
Omid Azimzadeh ◽  
Michael Rosemann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Potential Role ◽  
Dermal Fibroblasts ◽  
Adipose Derived Stem Cells ◽  
Mechanism Of Formation ◽  
Collagen Vi

The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

Commedia dell'arte Actresses and the Performance of Lovesickness

2009 ◽  
Vol 10 (2) ◽  
pp. 26-37
Author(s):  
Clarissa Hanora Hurley
Keyword(s):  
Medical Condition ◽  
Commedia Dell'arte ◽  
Cultural Attitudes ◽  
Gender Based

In the late sixteenth and early seventeenth centuries there was a conjunction of interest in erotomania as a “real” medical condition and the representation of that condition in literature and on the popular stage. This period corresponds with the rise of the professional actress of the commedia dell’arte. This paper explores some instances of pazzia (madness) scenes in the scenarios of Flaminio Scala and contemporary accounts of commedia performances with a view to better understanding the role of the professional theatre and professional actress in shaping and reflecting cultural attitudes towards gender-based erotic “distraction”.

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