THE CONTEXT
Cells interact with the extracellular matrix (ECM) through integrins. During wound repair, fibroblasts and myofibroblasts migrate, contract the wound, and synthesize connective tissue proteins.
Integrins connect attachment to signaling
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Integrins mediate attachment of cells to ECM constituents such as laminin and fibronectin, functionally and structurally linking the intracellular cytoskeleton to the extracellular environment.
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Integrins also mediate cell–cell adhesion.
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Binding through integrins provides focal attachment to underlying substrates and triggers signaling cascades that influence locomotion, proliferation, shape, and differentiation.
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Both epithelial and mesenchymal cells, including fibroblasts, interact with ECM through integrins.
Fibroblasts and wound contraction
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Cytokines and growth factors stimulate fibroblasts to enter the wound from its edges and migrate toward its center.
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Some fibroblasts differentiate into myofibroblasts, which contain smooth muscle actin and have increased contractile activity.
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Myofibroblasts help close wounds by pulling their margins toward the center.
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Activated fibroblasts and myofibroblasts increase synthesis of connective tissue proteins, mainly collagen and other ECM proteins.
Transforming growth factor-b
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Transforming growth factor-b (TGF-b)* is the most important cytokine for synthesis and deposition of connective tissue proteins.
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Most cells in granulation tissue, including activated macrophages, produce TGF-b.
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TGF-b stimulates fibroblast migration and proliferation and increases synthesis of collagen and fibronectin.
ECM organization
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The main ECM components include collagens, proteoglycans, and adhesive glycoproteins.
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Basement membranes and interstitial ECM differ in architecture and general composition, although some components occur in both.