-
Cardiovascular Research May 2021Myocardial fibrosis, the expansion of the cardiac interstitium through deposition of extracellular matrix proteins, is a common pathophysiologic companion of many... (Review)
Review
Myocardial fibrosis, the expansion of the cardiac interstitium through deposition of extracellular matrix proteins, is a common pathophysiologic companion of many different myocardial conditions. Fibrosis may reflect activation of reparative or maladaptive processes. Activated fibroblasts and myofibroblasts are the central cellular effectors in cardiac fibrosis, serving as the main source of matrix proteins. Immune cells, vascular cells and cardiomyocytes may also acquire a fibrogenic phenotype under conditions of stress, activating fibroblast populations. Fibrogenic growth factors (such as transforming growth factor-β and platelet-derived growth factors), cytokines [including tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-10, and IL-4], and neurohumoral pathways trigger fibrogenic signalling cascades through binding to surface receptors, and activation of downstream signalling cascades. In addition, matricellular macromolecules are deposited in the remodelling myocardium and regulate matrix assembly, while modulating signal transduction cascades and protease or growth factor activity. Cardiac fibroblasts can also sense mechanical stress through mechanosensitive receptors, ion channels and integrins, activating intracellular fibrogenic cascades that contribute to fibrosis in response to pressure overload. Although subpopulations of fibroblast-like cells may exert important protective actions in both reparative and interstitial/perivascular fibrosis, ultimately fibrotic changes perturb systolic and diastolic function, and may play an important role in the pathogenesis of arrhythmias. This review article discusses the molecular mechanisms involved in the pathogenesis of cardiac fibrosis in various myocardial diseases, including myocardial infarction, heart failure with reduced or preserved ejection fraction, genetic cardiomyopathies, and diabetic heart disease. Development of fibrosis-targeting therapies for patients with myocardial diseases will require not only understanding of the functional pluralism of cardiac fibroblasts and dissection of the molecular basis for fibrotic remodelling, but also appreciation of the pathophysiologic heterogeneity of fibrosis-associated myocardial disease.
Topics: Animals; Antifibrotic Agents; Cardiomyopathies; Extracellular Matrix; Fibroblasts; Fibrosis; Humans; Mechanotransduction, Cellular; Myocytes, Cardiac
PubMed: 33135058
DOI: 10.1093/cvr/cvaa324 -
Nature Reviews. Molecular Cell Biology Dec 2014The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves... (Review)
Review
The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.
Topics: Animals; Endopeptidases; Epithelial Cells; Extracellular Matrix; Fibrosis; Humans; Morphogenesis; Neoplasms
PubMed: 25415508
DOI: 10.1038/nrm3904 -
The FEBS Journal Dec 2021Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly... (Review)
Review
Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members of the ECM family. Proteins/glycoproteins, such as collagens, elastin, laminins and tenascins, proteoglycans and glycosaminoglycans, hyaluronan, and their cell receptors such as CD44 and integrins, responsible for cell adhesion, comprise a well-organized functional network with significant roles in health and disease. On the other hand, enzymes such as matrix metalloproteinases and specific glycosidases including heparanase and hyaluronidases contribute to matrix remodeling and affect human health. Several cell processes and functions, among them cell proliferation and survival, migration, differentiation, autophagy, angiogenesis, and immunity regulation are affected by certain matrix components. Structural alterations have been also well associated with disease progression. This guide on the composition and functions of the ECM gives a broad overview of the matrisome, the major ECM macromolecules, and their interaction networks within the ECM and with the cell surface, summarizes their main structural features and their roles in tissue organization and cell functions, and emphasizes the importance of specific ECM constituents in disease development and progression as well as the advances in molecular targeting of ECM to design new therapeutic strategies.
Topics: Animals; Extracellular Matrix; Humans
PubMed: 33605520
DOI: 10.1111/febs.15776 -
Nature Reviews. Molecular Cell Biology Dec 2014Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance... (Review)
Review
Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the ECM by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechanoregulation process, which includes the deposition, rearrangement or removal of the ECM to maintain overall form and function. Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.
Topics: Animals; Cytoskeleton; Extracellular Matrix; Homeostasis; Humans; Integrins; Mechanotransduction, Cellular
PubMed: 25355505
DOI: 10.1038/nrm3896 -
Journal of Cell Science Dec 2010
Review
Topics: Animals; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Homeostasis; Humans; Neoplasms
PubMed: 21123617
DOI: 10.1242/jcs.023820 -
Nature Reviews. Molecular Cell Biology Dec 2014The biochemical and biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. The molecules that are associated with the ECM of... (Review)
Review
The biochemical and biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. The molecules that are associated with the ECM of each tissue, including collagens, proteoglycans, laminins and fibronectin, and the manner in which they are assembled determine the structure and the organization of the resultant ECM. The product is a specific ECM signature that is comprised of unique compositional and topographical features that both reflect and facilitate the functional requirements of the tissue.
Topics: Animals; Basement Membrane; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Neurons; Proteoglycans
PubMed: 25370693
DOI: 10.1038/nrm3902 -
Frontiers of Medicine Feb 2022Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and... (Review)
Review
Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell-matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.
Topics: Cell Differentiation; Cell Proliferation; Decellularized Extracellular Matrix; Extracellular Matrix; Humans; Mesenchymal Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 34962624
DOI: 10.1007/s11684-021-0900-3 -
International Journal of Molecular... Oct 2018The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. The ECM is highly... (Review)
Review
The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. The ECM is highly dynamic as it is constantly deposited, remodelled, and degraded during development until maturity to maintain tissue homeostasis. The ECM's composition and organization are spatiotemporally regulated to control cell behaviour and differentiation, but dysregulation of ECM dynamics leads to the development of diseases such as cancer. The chemical cues presented by the ECM have been appreciated as key drivers for both development and cancer progression. However, the mechanical forces present due to the ECM have been largely ignored but recently recognized to play critical roles in disease progression and malignant cell behaviour. Here, we review the ways in which biophysical forces of the microenvironment influence biochemical regulation and cell phenotype during key stages of human development and cancer progression.
Topics: Animals; Carcinogenesis; Epithelial-Mesenchymal Transition; Extracellular Matrix; Humans; Tumor Microenvironment
PubMed: 30287763
DOI: 10.3390/ijms19103028 -
Developmental Cell May 2019The extracellular matrix is perturbed in tumors. The tumor matrix promotes the growth, survival, and invasion of the cancer and modifies fibroblast and immune cell... (Review)
Review
The extracellular matrix is perturbed in tumors. The tumor matrix promotes the growth, survival, and invasion of the cancer and modifies fibroblast and immune cell behavior to drive metastasis and impair treatment. Here, we discuss how the tumor matrix regulates metastasis by fostering tumor cell invasion into the stroma and migration toward the vasculature. We describe the role of the tumor matrix in cancer cell intravasation and vascular dissemination. We examine the impact of the matrix on disseminated tumor cell extravasation and on tumor dormancy and metastatic outgrowth. Finally, we discuss the clinical outcome of therapeutics that normalize tumor-matrix interactions.
Topics: Animals; Extracellular Matrix; Fibroblasts; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic
PubMed: 31063753
DOI: 10.1016/j.devcel.2019.03.026 -
The FEBS Journal Aug 2019Extracellular matrices (ECMs) are highly specialized and dynamic three-dimensional (3D) scaffolds into which cells reside in tissues. ECM is composed of a variety of... (Review)
Review
Extracellular matrices (ECMs) are highly specialized and dynamic three-dimensional (3D) scaffolds into which cells reside in tissues. ECM is composed of a variety of fibrillar components, such as collagens, fibronectin, and elastin, and non-fibrillar molecules as proteoglycans, hyaluronan, and glycoproteins including matricellular proteins. These macromolecular components are interconnected forming complex networks that actively communicate with cells through binding to cell surface receptors and/or matrix effectors. ECMs exert diverse roles, either providing tissues with structural integrity and mechanical properties essential for tissue functions or regulating cell phenotype and functions to maintain tissue homeostasis. ECM molecular composition and structure vary among tissues, and is markedly modified during normal tissue repair as well as during the progression of various diseases. Actually, abnormal ECM remodeling occurring in pathologic circumstances drives disease progression by regulating cell-matrix interactions. The importance of matrix molecules to normal tissue functions is also highlighted by mutations in matrix genes that give rise to genetic disorders with diverse clinical phenotypes. In this review, we present critical and emerging issues related to matrix assembly in tissues and the multitasking roles for ECM in diseases such as osteoarthritis, fibrosis, cancer, and genetic diseases. The mechanisms underlying the various matrix-based diseases are also discussed. Research focused on the highly dynamic 3D ECM networks will help to discover matrix-related causative abnormalities of diseases as well as novel diagnostic tools and therapeutic targets.
Topics: Animals; Carcinogenesis; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Humans; Osteoarthritis
PubMed: 30908868
DOI: 10.1111/febs.14818