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Remodelling the extracellular matrix in development and disease
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Journal Article
Remodelling the extracellular matrix in development and disease
2014
Overview
Key Points
The extracellular matrix (ECM) is a dynamic structure that is constantly remodelled to control tissue homeostasis.
The ECM in mammals is composed of around 300 proteins, known as the core matrisome.
Metalloproteinases are the main endopeptidases responsible for ECM degradation. These enzymes can also generate ECM fragments with different bioactive properties than their full-length proteins. These matrikines regulate many processes such as migration, adhesion and differentiation.
ECM remodelling is important during organogenesis and development of the intestine, mammary and salivary glands and lung.
Dysregulation of the ECM composition and structure and mutations in genes that affect ECM remodeling can lead to several severe human conditions, including fibrosis and cancer.
ECM components and the proteins that regulate ECM remodelling represent promising therapeutic targets. Additional preclinical and clinical studies are required to fully understand the role of the ECM in human disease.
The extracellular matrix (ECM) regulates many cellular functions, and its remodelling by enzymes such as metalloproteinases has a crucial role during development, as exemplified by intestinal, lung, mammary gland and submandibular gland morphogenesis. ECM structure and composition are important therapeutic targets, as their dysregulation contributes to conditions such as fibrosis and invasive cancer.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/67
/ Animals
/ Biochemistry, Molecular Biology
/ Collagen
/ Enzymes
/ Epithelial Cells - chemistry
/ Epithelial Cells - metabolism
/ Extracellular Matrix - chemistry
/ Extracellular Matrix - enzymology
/ Extracellular Matrix - metabolism
/ Extracellular Matrix - pathology
/ Humans
/ Ligands
/ Proteins
