This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
This review considers available data on the composition of the extracellular matrix (ECM) in echinoderms. The connective tissue in these animals has a rather complex organization. It includes a wide range of structural ECM proteins, as well as various proteases and their inhibitors. Members of almost all major groups of collagens, various glycoproteins, and proteoglycans have been found in echinoderms. There are enzymes for the synthesis of structural proteins and their modification by polysaccharides. However, the ECM of echinoderms substantially differs from that of vertebrates by the lack of elastin, fibronectins, tenascins, and some other glycoproteins and proteoglycans. Echinoderms have a wide variety of proteinases, with serine, cysteine, aspartic, and metal peptidases identified among them. Their active centers have a typical structure and can break down various ECM molecules. Echinoderms are also distinguished by a wide range of proteinase inhibitors. The complex ECM structure and the variety of intermolecular interactions evidently explain the complexity of the mechanisms responsible for variations in the mechanical properties of connective tissue in echinoderms. These mechanisms probably depend not only on the number of cross-links between the molecules, but also on the composition of ECM and the properties of its proteins.
Extracellular matrix interactions have essential roles in normal physiology and many pathological processes. Although the importance of extracellular matrix interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel-screening platform capable of measuring phenotypic responses to combinations of extracellular matrix molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the extracellular matrix-dependent adhesion of tumour-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumour lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8 or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified extracellular matrix and integrin interactions that could serve as therapeutic targets.
Extracellular matrixes (ECMs) are intricate 3-dimensional macromolecular networks of unique architectures with regulatory roles in cell morphology and functionality. As a dynamic native biomaterial, ECM undergoes constant but tightly controlled remodeling that is crucial for the maintenance of normal cellular behavior. Under pathological conditions like cancer, ECM remodeling ceases to be subjected to control resulting in disease initiation and progression. ECM is comprised of a staggering number of molecules that interact not only with one another, but also with neighboring cells via cell surface receptors. Such interactions, too many to tally, are of paramount importance for the identification of novel disease biomarkers and more personalized therapeutic intervention. Recent advances in big data analytics have allowed the development of online databases where researchers can take advantage of a stochastic evaluation of all the possible interactions and narrow them down to only those of interest for their study, respectively. This novel approach addresses the limitations that currently exist in studies, expands our understanding on ECM interactions, and has the potential to advance the development of targeted therapies. In this article we present the current trends in ECM biology research and highlight its importance in tissue integrity, the main interaction networks, ECM-mediated cell functional properties and issues related to pharmacological targeting.
A variety of approaches to understand extracellular matrix protein structure and function require production of recombinant proteins. Moreover, the expression of heterologous extracellular matrix proteins, in particular collagens, using the recombinant technology is of major interest to the biomedical industry. Although extracellular matrix proteins are large, modular and often multimeric, most of them have been successfully produced in various expression systems. This review provides important factors, including the design of the construct, the cloning strategies, the expression vectors, the transfection method and the host cell systems, to consider in choosing a reliable and cost-effective way to make recombinant extracellular matrix proteins. Advantages and drawbacks of each system have been appraised. Protocols that may ease efficient recombinant production of extracellular matrix are described. Emphasis is placed on the recombinant collagen production. Members of the collagen superfamily exhibit specific structural features and generally require complex post-translational modifications to retain full biological activity that make more arduous their recombinant production.
Extracellular matrices are essential for cellular and organismal function. Recent genome-wide and phenome-wide association studies started to reveal a broad spectrum of phenotypes associated with genetic variants. However, the phenome or spectrum of all phenotypes associated with genetic variants in extracellular matrix genes is unknown. Here, we analyzed over two million recorded genotype-to-phenotype relationships across multiple species to define their extracellular matrix phenomes. By using the previously defined matrisomes of humans, mice, zebrafish, Drosophila, and C. elegans, we found that the extracellular matrix phenome comprises of 3-10% of the entire phenome. Collagens (COL1A1, COL2A1) and fibrillin (FBN1) are each associated with >150 distinct phenotypes in humans, whereas collagen COL4A1, Wnt- and sonic hedgehog (shh) signaling are predominantly associated in other species. We determined the phenotypic fingerprints of matrisome genes and found that MSTN, CTSD, LAMB2, HSPG2, and COL11A2 and their corresponding orthologues have the most phenotypes across species. Out of the 42,551 unique matrisome genotype-to-phenotype relationships across the five species with defined matrisomes, we have constructed interaction networks to identify the underlying molecular components connecting with orthologues phenotypes and with novel phenotypes. Thus, our networks provide a framework to predict unassessed phenotypes and their potential underlying molecular interactions. These frameworks inform on matrisome genotype-to-phenotype relationships and potentially provide a sophisticated choice of biological model system to study human phenotypes and diseases.
Astrocytic injury responses are known to be influenced by the extracellular matrix (ECM). Astrocytes are also recognized as a source of extracellular vesicles (EVs) that can impact the activity and function of other astrocytes and cell types. Whether the ECM influences the function of astrocytic EVs in the context of wound recovery has not been previously studied. We report EVs from astrocytes cultured on varied ECM substrates are sufficient to elicit distinct injury responses in naive astrocytes that recapitulate the effects of the ECM of origin. When compared with wound recovery on control substrates, EVs from ECM-exposed astrocytes elicited accelerated rates of wound recovery that varied based on each ECM. When EVs were collected from IL-1β treated and ECM-exposed astrocyte cultures, we found that IL-1β arrested wound recovery in naive astrocytes treated with EVs from astrocytes cultured on ECM but adding EVs from IL-1β treated Tenascin-c-cultured astrocytes increased wound recovery. To confirm that ECM was a primary influence on these astrocytic EV functions, we tested the contribution of β1-integrin, a major integrin receptor for the ECM molecules tested in this study. We found that the β1-integrin inhibitor Ha2/5, resulted in EVs that significantly attenuated the wound recovery of naive astrocytes. This provides new information on the importance of culture substrates on astrocytic responses, EV functions and injury responses that may impact the understanding of astroglial responses related to ECM compositional differences in diverse physiological states.
The extracellular matrix (ECM) is a highly-dynamic compartment that undergoes remodeling as a result of injury and repair. Over the past decade, mounting evidence in humans and rodents suggests that ECM remodeling is associated with diet-induced insulin resistance in several metabolic tissues. In addition, integrin receptors for the ECM have also been implicated in the regulation of insulin action. This review addresses what is currently known about the ECM, integrins, and insulin action in the muscle, liver, and adipose tissue. Understanding how ECM remodeling and integrin signaling regulate insulin action may aid in the development of new therapeutic targets for the treatment of insulin resistance and type 2 diabetes (T2D).
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy, and surgical resection; nevertheless, little to no improvement in long term survival has been achieved in decades-underlining the need for target discovery and new therapeutic approaches to targeting tumor cells or the tumor microenvironment. To evaluate cross-species sarcoma extracellular matrix production, we have used murine models which feature knowledge of the myogenic cell-of-origin. With focus on the RMS/undifferentiated pleomorphic sarcoma (UPS) continuum, we have constructed tissue microarrays of 48 murine and four human sarcomas to analyze expression of seven different collagens, fibrillins, and collagen-modifying proteins, with cross-correlation to RNA deep sequencing. We have uncovered that RMS produces increased expression of type XVIII collagen alpha 1 (COL18A1), which is clinically associated with decreased long-term survival. We have also identified significantly increased RNA expression of COL4A1, FBN2, PLOD1, and PLOD2 in human RMS relative to normal skeletal muscle. These results complement recent studies investigating whether soft tissue sarcomas utilize collagens, fibrillins, and collagen-modifying enzymes to alter the structural integrity of surrounding host extracellular matrix/collagen quaternary structure resulting in improved ability to improve the ability to invade regionally and metastasize, for which therapeutic targeting is possible.
MatrixDB (http://matrixdb.ibcp.fr) is a freely available database focused on interactions established by extracellular proteins and polysaccharides. Only few databases report protein-polysaccharide interactions and, to the best of our knowledge, there is no other database of extracellular interactions. MatrixDB takes into account the multimeric nature of several extracellular protein families for the curation of interactions, and reports interactions with individual polypeptide chains or with multimers, considered as permanent complexes, when appropriate. MatrixDB is a member of the International Molecular Exchange consortium (IMEx) and has adopted the PSI-MI standards for the curation and the exchange of interaction data. MatrixDB stores experimental data from our laboratory, data from literature curation, data imported from IMEx databases, and data from the Human Protein Reference Database. MatrixDB is focused on mammalian interactions, but aims to integrate interaction datasets of model organisms when available. MatrixDB provides direct links to databases recapitulating mutations in genes encoding extracellular proteins, to UniGene and to the Human Protein Atlas that shows expression and localization of proteins in a large variety of normal human tissues and cells. MatrixDB allows researchers to perform customized queries and to build tissue- and disease-specific interaction networks that can be visualized and analyzed with Cytoscape or Medusa.
The higher-order patterning of extra-cellular matrix in normal and pathological tissues has profound consequences on tissue function. Whilst studies have documented both how fibroblasts create and maintain individual matrix fibers and how cell migration is altered by the fibers they interact with, a model unifying these two aspects of tissue organization is lacking. Here we use computational modelling to understand the effect of this interconnectivity between fibroblasts and matrix at the mesoscale level. We created a unique adaptation to the Vicsek flocking model to include feedback from a second layer representing the matrix, and use experimentation to parameterize our model and validate model-driven hypotheses. Our two-layer model demonstrates that feedback between fibroblasts and matrix increases matrix diversity creating higher-order patterns. The model can quantitatively recapitulate matrix patterns of tissues in vivo. Cells follow matrix fibers irrespective of when the matrix fibers were deposited, resulting in feedback with the matrix acting as temporal 'memory' to collective behaviour, which creates diversity in topology. We also establish conditions under which matrix can be remodelled from one pattern to another. Our model elucidates how simple rules defining fibroblast-matrix interactions are sufficient to generate complex tissue patterns.
Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins, and their large size (∼30-150 nm) limits diffusion. We isolated EVs from the MCF10 series-a model human cell line of breast cancer progression-and demonstrated increasing presence of laminin-binding integrins α3β1 and α6β1 on the EVs as the malignant potential of the MCF10 cells increased. Transport of the EVs within a microfluidic device under controlled physiological interstitial flow (0.15-0.75 μm/s) demonstrated that convection was the dominant mechanism of transport. Binding of the EVs to the ECM enhanced the spatial concentration and gradient, which was mitigated by blocking integrins α3β1 and α6β1. Our studies demonstrate that convection and ECM binding are the dominant mechanisms controlling EV interstitial transport and should be leveraged in nanotherapeutic design.
The cell-derived extracellular matrix (ECM) is associated with a lower risk of pathogen transfer, and it possesses an ideal niche with growth factors and complex fibrillar proteins for cell attachment and growth. However, the cell-derived ECM is found to have poor biomechanical properties, and processing of cell-derived ECM into gels is scarcely studied. The gel provides platforms for three-dimensional cell culture, as well as injectable biomaterials, which could be delivered via a minimally invasive procedure. Thus, in this study, an adipose-derived stem cell (ADSC)-derived ECM gel was developed and cross-linked by genipin to address the aforementioned issue. The genipin cross-linked ADSC ECM gel was fabricated via several steps, including rabbit ADSC culture, cell sheets, decellularization, freeze-thawing, enzymatic digestion, neutralization of pH, and cross-linking. The physicochemical characteristics and cytocompatibility of the gel were evaluated. The results demonstrated that the genipin cross-linking could significantly enhance the mechanical properties of the ADSC ECM gel. Furthermore, the ADSC ECM was found to contain collagen, fibronectin, biglycan, and transforming growth factor (TGF)-β1, which could substantially maintain ADSC, skin, and ligament fibroblast cell proliferation. This cell-derived natural material could be suitable for future regenerative medicine and tissue engineering application.
The extracellular matrix (ECM) is the scaffold that provides structure and support to all organs, including the lung; however, it is also much more than this. The ECM provides biochemical and biomechanical cues to cells that reside or transit through this micro-environment, instructing their responses. The ECM structure and composition changes in chronic lung diseases; how such changes impact disease pathogenesis is not as well understood. Cells bind to the ECM through surface receptors, of which the integrin family is one of the most widely recognised. The signals that cells receive from the ECM regulate their attachment, proliferation, differentiation, inflammatory secretory profile and survival. There is extensive evidence documenting changes in the composition and amount of ECM in diseased lung tissues. However, changes in the topographical arrangement, organisation of the structural fibres and stiffness (or viscoelasticity) of the matrix in which cells are embedded have an undervalued but strong impact on cell phenotype. The ECM in diseased lungs also changes in physical and biomechanical ways that drive cellular responses. The characteristics of these environments alter cell behaviour and potentially orchestrate perpetuation of lung diseases. Future therapies should target ECM remodelling as much as the underlying culprit cells.
Periostin, originally named osteoblast-specific factor 2 (OSF-2) has been identified primarily in collagen rich, biomechanically active tissues where its role has been implicated in mechanisms to maintain the extracellular matrix (ECM), including collagen fibrillogenesis and crosslinking. It is well documented that periostin plays a role in wound healing and scar formation after injury, in part, by promoting cell proliferation, myofibroblast differentiation, and/or collagen fibrillogenesis. Given the significance of periostin in other scar forming models, we hypothesized that periostin will influence Achilles tendon healing by modulating ECM production. Therefore, the objective of this study was to elucidate the effects of periostin during Achilles tendon healing using periostin homozygous (Postn -/-) and heterozygous (Postn +/-) mouse models. A second experiment was included to further examine the influence of periostin on collagen composition and function using intact dorsal tail tendons. Overall, Postn -/- and Postn +/- Achilles tendons exhibited impaired healing as demonstrated by delayed wound closure, increased type III collagen production, decreased cell proliferation, and reduced tensile strength. Periostin ablation also reduced tensile strength and stiffness, and altered collagen fibril distribution in the intact dorsal tail tendons. Achilles tendon outcomes support our hypothesis that periostin influences healing, while tail tendon results indicate that periostin also affects ECM morphology and behavior in mouse tendons.
Extracellular matrix (ECM) remodeling is a key physiological process that occurs in a number of contexts, including cell migration, and is especially important for cellular form and function in three-dimensional (3D) matrices. However, there have been few attempts to computationally model how cells modify their environment in a manner that accounts for both cellular properties and the architecture of the surrounding ECM. To this end, we have developed and validated a novel model to simulate matrix remodeling that explicitly defines cells in a 3D collagenous matrix. In our simulation, cells can degrade, deposit, or pull on local fibers, depending on the fiber density around each cell. The cells can also move within the 3D matrix. Different cell phenotypes can be modeled by varying key cellular parameters. Using the model we have studied how two model cancer cell lines, of differing invasiveness, modify matrices with varying fiber density in their vicinity by tracking the metric of fraction of matrix occupied by fibers. Our results quantitatively demonstrate that in low density environments, cells deposit more collagen to uniformly increase fibril fraction. On the other hand, in higher density environments, the less invasive model cell line reduced the fibril fraction as compared to the highly invasive phenotype. These results show good qualitative and quantitative agreement with existing experimental literature. Our simulation is therefore able to function as a novel platform to provide new insights into the clinically relevant and physiologically critical process of matrix remodeling by helping identify critical parameters that dictate cellular behavior in complex native-like environments.
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and liver fibrosis. The scope of the present study was to develop a novel enzyme-linked immunosorbent assay (ELISA) for the measurement of a MMP-9 and MMP-12-generated biglycan neo-epitope and to test its biological validity in a rat model of RA and in two rat models of liver fibrosis, chosen as models of ECMR.
The extracellular matrix undergoes extensive remodeling during hepatocellular carcinoma and functions as a critical component of the tumor microenvironment by providing a substratum for cell adhesion and serving as a reservoir for a variety of cytokines and growth factors. Despite the clinical correlation between ECM deposition and hepatocellular carcinoma progression, it remains unclear how global extracellular matrix gene expression is altered in hepatocellular carcinoma and the molecular pathways that govern this change. Herein, a comprehensive analysis of the extracellular matrix transcriptome using an RNA-sequencing dataset provided by The Cancer Genome Atlas consortium was conducted and indicates substantial differential gene expression of key extracellular matrix collagens, glycoproteins, and proteoglycans in hepatocellular carcinoma. This analysis also reveals alternative expression of extracellular matrix gene transcript variants that could impact biological activity and serves as a framework for exploring the dynamic nature of the extracellular matrix transcriptome in cancer and identifying candidate genes for future exploration.
Ideal scaffolds that represent native extracellular matrix (ECM) properties of musculofascial tissues have great importance in musculofascial tissue engineering. However, detailed characterization of musculofascial tissues' ECM (particularly, of fascia) from large animals is still lacking. In this study, we developed a decellularization protocol for processing pig composite musculofascial tissues. Decellularized muscle (D-muscle) and decellularized fascia (D-fascia), which are two important components of decellularized musculofascial extracellular matrix (DMM), were comprehensively characterized. D-muscle and D-fascia retained intact three-dimensional architecture, strong mechanical properties, and bioactivity of compositions such as collagen, laminin, glycosaminoglycan, and vascular endothelial growth factor. D-muscle and D-fascia provided a compatible niche for human adipose-derived stem cell integration and proliferation. Heterotopic and orthotopic implantation of D-muscle and D-fascia in a rodent model further proved their biocompatibility and myogenic properties during the remodeling process. The differing characteristics of D-muscle from D-fascia (e.g. D-muscle's strong pro-angiogenic and pro-myogenic properties vs. D-fascia's strong mechanical properties) indicate different clinical application opportunities of D-muscle vs. D-fascia scaffolds. DMM comprising muscle and fascia ECM as a whole unit can thus provide not only a clinically translatable platform for musculofascial tissue repair and regeneration but also a useful standard for scaffold design in musculofascial tissue engineering.
In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity. The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs), and the specific role of PNNs on neural plasticity remains elusive. Here, we genetically targeted the Acan gene encoding for aggrecan using a novel animal model. This allowed for conditional and targeted loss of aggrecan in vivo, which ablated the PNN structure and caused a shift in the population of parvalbumin-expressing inhibitory interneurons toward a high plasticity state. Selective deletion of the Acan gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity, which was mechanistically identical to critical period plasticity. Brain-wide targeting improved object recognition memory.SIGNIFICANCE STATEMENT The study provides the first direct evidence of aggrecan as the main functional constituent and orchestrator of perineuronal nets (PNNs), and that loss of PNNs by aggrecan removal induces a permanent state of critical period-like plasticity. Loss of aggrecan ablates the PNN structure, resulting in invoked juvenile plasticity in the visual cortex and enhanced object recognition memory.
The formation and maintenance of connectivity are critically important for the processing and storage of information in neuronal networks. The brain extracellular matrix (ECM) appears during postnatal development and surrounds most neurons in the adult mammalian brain. Importantly, the removal of the ECM was shown to improve plasticity and post-traumatic recovery in the CNS, but little is known about the mechanisms. Here, we investigated the role of the ECM in the regulation of the network activity in dissociated hippocampal cultures grown on microelectrode arrays (MEAs). We found that enzymatic removal of the ECM in mature cultures led to transient enhancement of neuronal activity, but prevented disinhibition-induced hyperexcitability that was evident in age-matched control cultures with intact ECM. Furthermore, the ECM degradation followed by disinhibition strongly affected the network interaction so that it strongly resembled the juvenile pattern seen in naïve developing cultures. Taken together, our results demonstrate that the ECM plays an important role in retention of existing connectivity in mature neuronal networks that can be exerted through synaptic confinement of glutamate. On the other hand, removal of the ECM can play a permissive role in modification of connectivity and adaptive exploration of novel network architecture.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: