Connective tissue remodeling: cross-talk between endothelins and matrix metalloproteinases. 2005

David Abraham, and Markella Ponticos, and Hideaki Nagase
Centre for Rheumatology and Connective Tissue Diseases, Department of Medicine, Royal Free and University College Medical School, London, UK. dabraham@medsch.ucl.ac.uk

Connective tissue remodeling is achieved by a complex process involving several cell types, a plethora of growth factors, cytokines, chemokines and turnover of extracellular matrix (ECM). The main enzymes that degrade ECM molecules are matrix metalloproteinases (MMPs) and their activities are regulated by endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recent studies have indicated that endothelins and their receptor expression affects tissue remodeling and repair. Endothelins are rapidly produced by endothelial cells in response to tissue injury and they have potent vasoconstrictive properties. They also promote tissue remodeling through activation of resident connective tissue cells and controlling the production of MMPs and TIMPs by the activated cells. In this review we present the cross-talk between the endothelins and the MMP-TIMP system and their implications in controlling the normal and abnormal tissue remodeling.

UI MeSH Term Description Entries
D012038 Regeneration The physiological renewal, repair, or replacement of tissue. Endogenous Regeneration,Regeneration, Endogenous,Regenerations
D003238 Connective Tissue Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX. Connective Tissues,Tissue, Connective,Tissues, Connective
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016232 Endothelins 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. Endothelium-Derived Vasoconstrictor Factors,Endothelin,Vasoconstrictor Factors, Endothelium-Derived
D017466 Receptors, Endothelin Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells. Endothelin Receptors,Receptors, Endothelium-Derived Vasoconstrictor Factor,Endothelin Receptor,Endothelium Derived Vasoconstrictor Factor Receptors,Receptors, Endothelins,Receptor, Endothelin,Receptors, Endothelium Derived Vasoconstrictor Factor
D019714 Tissue Inhibitor of Metalloproteinases A family of secreted protease inhibitory proteins that regulates the activity of SECRETED MATRIX METALLOENDOPEPTIDASES. They play an important role in modulating the proteolysis of EXTRACELLULAR MATRIX, most notably during tissue remodeling and inflammatory processes. Tissue Inhibitor of Metalloproteinase,TIMP Proteins,Metalloproteinase Tissue Inhibitor,Metalloproteinases Tissue Inhibitor,Proteins, TIMP
D020782 Matrix Metalloproteinases A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components. MMP,MMPs,Matrix Metalloproteinase,Metalloproteinase, Matrix,Metalloproteinases, Matrix

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