Exploring the extracellular matrix in health and disease using proteomics

2019 ◽  
Vol 63 (3) ◽  
pp. 417-432 ◽  
Author(s):  
Isra N. Taha ◽  
Alexandra Naba
Keyword(s):  
Extracellular Matrix ◽  
Protein Production ◽  
Protein Composition ◽  
Protein Assembly ◽  
Mechanical Support ◽  
Cellular Processes ◽  
Potential Reservoir ◽  
Health And Disease ◽  
Multicellular Organisms ◽  
Biochemical Signals

Abstract The extracellular matrix (ECM) is a complex assembly of hundreds of proteins that constitutes the scaffold of multicellular organisms. In addition to providing architectural and mechanical support to the surrounding cells, it conveys biochemical signals that regulate cellular processes including proliferation and survival, fate determination, and cell migration. Defects in ECM protein assembly, decreased ECM protein production or, on the contrary, excessive ECM accumulation, have been linked to many pathologies including cardiovascular and skeletal diseases, cancers, and fibrosis. The ECM thus represents a potential reservoir of prognostic biomarkers and therapeutic targets. However, our understanding of the global protein composition of the ECM and how it changes during pathological processes has remained limited until recently. In this mini-review, we provide an overview of the latest methodological advances in sample preparation and mass spectrometry-based proteomics that have permitted the profiling of the ECM of now dozens of normal and diseased tissues, including tumors and fibrotic lesions.

scholarly journals A novel Microproteomic Approach Using Laser Capture Microdissection to Study Cellular Protrusions

2019 ◽  
Vol 20 (5) ◽  
pp. 1172 ◽  
Author(s):  
Karine Gousset ◽  
Ana Gordon ◽  
Shravan Kumar Kannan ◽  
Joey Tovar
Keyword(s):  
Laser Capture Microdissection ◽  
Protein Extraction ◽  
Cell Communication ◽  
Protein Composition ◽  
Fluorescent Markers ◽  
Different Types ◽  
Health And Disease ◽  
Multicellular Organisms ◽  
First Time ◽  
Laser Capture

Cell–cell communication is vital to multicellular organisms, and distinct types of cellular protrusions play critical roles during development, cell signaling, and the spreading of pathogens and cancer. The differences in the structure and protein composition of these different types of protrusions and their specific functions have not been elucidated due to the lack of a method for their specific isolation and analysis. In this paper, we described, for the first time, a method to specifically isolate distinct protrusion subtypes, based on their morphological structures or fluorescent markers, using laser capture microdissection (LCM). Combined with a unique fixation and protein extraction protocol, we pushed the limits of microproteomics and demonstrate that proteins from LCM-isolated protrusions can successfully and reproducibly be identified by mass spectrometry using ultra-high field Orbitrap technologies. Our method confirmed that different types of protrusions have distinct proteomes and it promises to advance the characterization and the understanding of these unique structures to shed light on their possible role in health and disease.

Cardiac myocytes cultured on a basement membrane extract of the ehs tumor

1986 ◽  
Vol 44 ◽  
pp. 270-271
Author(s):  
L. Terracio ◽  
A. Dewey ◽  
K. Rubin ◽  
T.K. Borg
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Cardiac Myocytes ◽  
Normal Tissue ◽  
Cell Spreading ◽  
Collagen Iv ◽  
Basement Membrane Extract ◽  
Membrane Extract ◽  
Growth Development ◽  
Multicellular Organisms

The recognition and interaction of cells with the extracellular matrix (ECM) effects the normal physiology as well as the pathology of all multicellular organisms. These interactions have been shown to influence the growth, development, and maintenance of normal tissue function. In previous studies, we have shown that neonatal cardiac myocytes specifically interacts with a variety of ECM components including fibronectin, laminin, and collagens I, III and IV. Culturing neonatal myocytes on laminin and collagen IV induces an increased rate of both cell spreading and sarcomerogenesis.

scholarly journals Maternal Uterine Vascular Remodeling During Pregnancy

Physiology ◽  
2009 ◽  
Vol 24 (1) ◽  
pp. 58-71 ◽  
Author(s):  
George Osol ◽  
Maurizio Mandala
Keyword(s):  
Extracellular Matrix ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Normal Pregnancy ◽  
Uterine Blood Flow ◽  
Growth And Remodeling ◽  
Cellular Mechanisms ◽  
Cellular Processes ◽  
Uteroplacental Blood Flow ◽  
Uterine Circulation

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

scholarly journals A Potential of microRNAs for High-Content Screening

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Andrius Serva ◽  
Christoph Claas ◽  
Vytaute Starkuviene
Keyword(s):  
Large Scale ◽  
Cellular Processes ◽  
Comprehensive Knowledge ◽  
Functional Models ◽  
Rapid Accumulation ◽  
Health And Disease ◽  
Temporal And Spatial ◽  
And Function ◽  
Functional Analyses ◽  
Immense Potential

In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.

Integrative view of serpins in health and disease: the contribution of serpinA3

2020 ◽  
Author(s):  
Andrea Sanchez-Navarro ◽  
Isaac González-Soria ◽  
Rebecca Caldiño-Bohn ◽  
Norma A. Bobadilla
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cellular Processes ◽  
Hormone Transport ◽  
Integrative View ◽  
Health And Disease ◽  
The Brain ◽  
Regulation Of Blood Pressure ◽  
Common Function

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular, and kidney disorders are intensively studied to find effective therapeutic targets. Given serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin have been associated with diverse pathophysiological events. In particular, we will focus on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes, as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.

scholarly journals Temperature-induced reorganisation of Schistocephalus solidus (Cestoda) proteome during the transition to the warm-blooded host

Biology Open ◽  
2021 ◽  
Vol 10 (11) ◽  
Author(s):  
Ekaterina V. Borvinskaya ◽  
Albina A. Kochneva ◽  
Polina B. Drozdova ◽  
Olga V. Balan ◽  
Victor G. Zgoda
Keyword(s):  
Model Experiment ◽  
Protein Production ◽  
Culture Medium ◽  
Gasterosteus Aculeatus ◽  
Protein Composition ◽  
Tegument Protein ◽  
Schistocephalus Solidus ◽  
Induced Genes

ABSTRACT The protein composition of the cestode Schistocephalus solidus was measured in an experiment simulating the trophic transmission of the parasite from a cold-blooded to a warm-blooded host. The first hour of host colonisation was studied in a model experiment, in which sticklebacks Gasterosteus aculeatus infected with S. solidus were heated at 40°C for 1 h. As a result, a decrease in the content of one tegument protein was detected in the plerocercoids of S. solidus. Sexual maturation of the parasites was initiated in an experiment where S. solidus larvae were taken from fish and cultured in vitro at 40°C for 48 h. Temperature-independent changes in the parasite proteome were investigated by incubating plerocercoids at 22°C for 48 h in culture medium. Analysis of the proteome allowed us to distinguish the temperature-induced genes of S. solidus, as well as to specify the molecular markers of the plerocercoid and adult worms. The main conclusion of the study is that the key enzymes of long-term metabolic changes (glycogen consumption, protein production, etc.) in parasites during colonisation of a warm-blooded host are induced by temperature.

scholarly journals Regulation of cellular functions by extracellular matrix.

1992 ◽  
Vol 2 (10) ◽  
pp. S83 ◽  
Author(s):  
A Teti
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor Receptor ◽  
Matrix Proteins ◽  
Intercellular Spaces ◽  
Cellular Functions ◽  
Proliferation And Differentiation ◽  
Alpha Beta ◽  
Covalently Linked ◽  
Multicellular Organisms ◽  
Specific Ligand

Multicellular organisms are formed by specialized cells assembled in tissues. Individual cells contact and interact with other cells and with the extracellular matrix--a network of secreted proteins and carbohydrates that fills the intercellular spaces. The extracellular matrix helps cells to bind together and regulates a number of cellular functions, such as adhesion, migration, proliferation, and differentiation. It is formed by macromolecules, locally secreted by resident cells. The two main classes of macromolecules are polysaccharide glycosaminoglycans, usually covalently linked to proteins in the form of proteoglycans, and fibrous proteins of two functional types, structural (collagen, elastin) and adhesive (fibronectin, laminin, vitronectin, etc.). Receptors for extracellular matrix macromolecules are present in virtually all of the cells studied. They belong to the superfamily of integrins, alpha beta heterodimers, which, in most cases, recognize the Arg-Gly-Asp sequence of extracellular matrix proteins. On the exterior side of the cell, integrins link an extracellular matrix macromolecule, whereas in the cytosol, they bind the cytoskeleton, thereby forming a membrane bridge between extracellular and intracellular fibers. This structure enables the cell to adhere to the substratum. Similar to hormone- or growth factor-receptor binding, the interaction of the integrin with its specific ligand induces immediate signal transduction and influences cellular activities.

Artificial protein assemblies with well-defined supramolecular protein nanostructures

2021 ◽  
Author(s):  
Suyeong Han ◽  
Yongwon Jung
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
Building Blocks ◽  
Protein Assembly ◽  
Protein Assemblies ◽  
Cellular Processes ◽  
Wide Range ◽  
Array Structures ◽  
Small Chemical ◽  
Artificial Protein

Nature uses a wide range of well-defined biomolecular assemblies in diverse cellular processes, where proteins are major building blocks for these supramolecular assemblies. Inspired by their natural counterparts, artificial protein-based assemblies have attracted strong interest as new bio-nanostructures, and strategies to construct ordered protein assemblies have been rapidly expanding. In this review, we provide an overview of very recent studies in the field of artificial protein assemblies, with the particular aim of introducing major assembly methods and unique features of these assemblies. Computational de novo designs were used to build various assemblies with artificial protein building blocks, which are unrelated to natural proteins. Small chemical ligands and metal ions have also been extensively used for strong and bio-orthogonal protein linking. Here, in addition to protein assemblies with well-defined sizes, protein oligomeric and array structures with rather undefined sizes (but with definite repeat protein assembly units) also will be discussed in the context of well-defined protein nanostructures. Lastly, we will introduce multiple examples showing how protein assemblies can be effectively used in various fields such as therapeutics and vaccine development. We believe that structures and functions of artificial protein assemblies will be continuously evolved, particularly according to specific application goals.

scholarly journals The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

2019 ◽  
Vol 106 ◽  
pp. 49-56 ◽  
Author(s):  
Natalia Sánchez-Romero ◽  
Pilar Sainz-Arnal ◽  
Iris Pla-Palacín ◽  
Pablo Royo Dachary ◽  
Helen Almeida ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Dynamic Relationship ◽  
Health And Disease

scholarly journals Skin proteomics – analysis of the extracellular matrix in health and disease

2020 ◽  
Vol 17 (5) ◽  
pp. 377-391
Author(s):  
Jörn Dengjel ◽  
Leena Bruckner-Tuderman ◽  
Alexander Nyström
Keyword(s):  
Extracellular Matrix ◽  
Proteomics Analysis ◽  
Health And Disease
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