Collagens are the most abundant components of the extracellular matrix and many types of soft tissues.
Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds.
Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between
cell surface receptors, e.g.,
integrins, and compounds such
collagen,
proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of
fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of
fibrinogen is in clot formation, after conversion to
fibrin by
thrombin, it also binds to a variety of compounds, particularly to various
growth factors, and as such
fibrinogen is a player in cardiovascular and extracellular matrix physiology.
Elastin, an insoluble
polymer of the monomeric soluble precursor
tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with
fibrillin microfibrils.
Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the
elastin gene lead to
cutis laxa.
Fibrillins represent the predominant core of the microfibrils in elastic as well as non-elastic extracellular matrixes, and interact closely with
tropoelastin and
integrins. Not only do microfibrils provide structural integrity of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues.
Fibrillin is important for the assembly of
elastin into elastic fibers. Mutations in the
fibrillin-1 gene are closely associated with
Marfan syndrome. Fibulins are tightly connected with basement membranes, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic
glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos,
heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of
thrombospondin 1 is activation of TGFβ. Increased expression of
thrombospondin and TGFβ activity was observed in fibrotic skin disorders such as
keloids and scleroderma.
Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic
scars and
systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in
atherosclerotic plaques as well.