Fig. 1.16C ). This can initiate the production of intracellular messengers or can directly trans-duce signals to the nucleus. Cell surface receptors for growth factors can activate signal transduction pathways that overlap with those mediated through integrins. Signals from ECM components and growth factors can be integrated by the cells to produce a given response, including changes in proliferation, locomotion, and/or differentiation.
for a variety of latent growth factors that can be activated within a focus of injury or inflammation.
Scaffolding for tissue renewal. Because maintenance of normal tissue structure requires a basement membrane or stromal scaffold, the integrity of the basement membrane or the stroma of parenchymal cells is critical for the organized regeneration of tissues. Thus, ECM disruption results in defective tissue regeneration and repair, for example, cirrhosis of the liver resulting from the collapse of the hepatic stroma in various forms of hepatitis.
Establishment of tissue microenvironments. The basement membrane acts as a boundary between the epithelium and underlying connective tissue; it does not just provide support to the epithelium but is also functional, for example, in the kidney, forming part of the filtration apparatus.
The ECM is constantly being remodeled; its synthesis and degradation accompany morphogenesis, tissue regeneration and repair, chronic fibrosis, and tumor invasion and metastasis. ECM occurs in two basic forms: interstitial matrix and basement membrane (
Fig. 1.14
Interstitial matrix is present in the spaces between cells in connective tissue, and between the parenchymal epithelium and the underlying supportive vascular and smooth muscle structures. The interstitial matrix is synthesized by mesenchymal cells (e.g., fibroblasts), forming an amorphous three-dimensional gel. Its major constituents are fibrillar and nonfibrillar collagens, as well as fibronectin, elastin, proteoglycans, hyaluronate, and other constituents (see later).
Basement membrane. The seemingly random array of interstitial matrix in connective tissues becomes highly organized around epithelial cells, endothelial cells, and smooth muscle cells, forming the specialized basement membrane. This is synthesized conjointly by the overlying epithelium and the underlying mesenchymal cells, forming a flat lamellar “chicken wire” mesh (although labeled as a membrane, it is quite porous). The major constituents are amorphous nonfibrillar type IV collagen and laminin.)
The components of the ECM fall into three groups of proteins (
Fig. 1.15
Fibrous structural proteins such as collagens and elastins that confer tensile strength and recoil
Water-hydrated gels such as proteoglycans and hyaluronan that permit compressive resistance and lubrication
Adhesive glycoproteins that connect ECM elements to one another and to cells
Collagens. Collagens are composed of three separate polypeptide chains braided into a ropelike triple helix. About 30 collagen types have been identified, some of which are unique to specific cells and tissues.
Some collagen types (e.g., types I, II, III, and V collagens) form linear fibrils stabilized by interchain hydrogen bonding; such fibrillar collagens form a major proportion of the connective tissue in structures such as bone, tendon, cartilage, blood vessels, and skin, as well as in healing wounds and scars. The tensile strength of the fibrillar collagens derives from lateral crosslinking of the triple helices by covalent bonds, an unusual