Extracellular matrix functions, forms, and contribution to fibrosis
THE CONTEXT
The extracellular matrix (ECM) regulates cell behavior and* supplies the structural scaffold needed for regeneration. Persistent injury can instead lead to replacement of normal tissue by connective tissue.
Regulation of proliferation and regeneration
•
The ECM controls cell proliferation by binding and displaying growth factors and signaling through integrin receptors.
•
It stores latent growth factors that can be activated at sites of injury or inflammation.
•
Regeneration requires an intact scaffold: basement membrane in epithelia and stroma in parenchymal organs.
Interstitial matrix and basement membrane
•
The ECM occurs in two basic forms: interstitial matrix and basement membrane.
•
Interstitial matrix occupies spaces between connective tissue cells and lies between epithelium and underlying vascular and smooth muscle structures in parenchymal organs.
•
Its major constituents include fibrillar and nonfibrillar collagens, fibronectin, elastin, proteoglycans, and hyaluronate.
•
Basement membrane is a highly organized matrix around epithelial, endothelial, and smooth muscle cells. Its major constituents are amorphous nonfibrillar type IV collagen and laminin.
•
Collagen is the major ECM component of interstitial matrix and scar tissue.
Persistent injury and connective tissue replacement
•
Persistent tissue injury causes chronic inflammation and loss of tissue architecture.
•
Cytokines from macrophages and other leukocytes stimulate migration and proliferation of fibroblasts and myofibroblasts, together with deposition of collagen and other ECM proteins.
•
The net result is replacement of normal tissue by connective tissue.