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Essential Role of Extracellular Matrix in Tissue
Formation and Maintenance
The extracellular
matrix (ECM) is a complex mixture of proteins and polysaccharides located
outside cells that provides structural and biochemical support to surrounding
cells. It is secreted locally by resident cells and undergoes constant
remodeling. The major components of extracellular matrix include collagen,
elastin, fibronectin and proteoglycans.
Components of Extracellular Matrix
Collagen- Collagen is the most abundant protein in the Extracellular
Matrix and forms strong fibrous structures that provide tensile
strength and scaffolding for cells to reside in. There are over 20 types of
collagen identified but types I, II, III are most prevalent.
Elastin- Elastin allows tissues to stretch and recoil through elastic fibers
that withstand mechanical forces. This enables tissues like skin, lungs and
blood vessels to extend and contract repeatedly.
Fibronectin- Fibronectin is a glycoprotein that binds collagen, fibrin and
cells to support cell attachment, migration and differentiation during wound
healing and development.
Proteoglycans- Proteoglycans like hyaluronic acid, decorin and versican
regulate cell adhesion, division and migration through their hydrated gel-like
extracellular environment and ability to bind growth factors.
Roles of Extracellular Matrix
provides physical scaffolding and structural support for cells and tissues
mediates cell-cell and cell-matrix interactions through integrin receptor
binding
acts as a reservoir for growth factors and cytokines that regulate tissue
repair, development and immunity
transmits force and mechanical signals between neighboring cells
regulates cell proliferation, migration and differentiation during development
and disease
ECM in Development and Maintenance of
Tissues
During embryonic development, the ECM composition changes dynamically as new
tissues form and differentiate. It specifies positional cues that direct cell
fate decisions through local biochemical and biomechanical signals. In the
adult, it provides the proper microenvironment for homeostasis and repair of
tissues after injury.
Some key roles of ECM include:
Bone - Collagens, elastin and proteoglycans allow bones to resist tensile and
compressive forces through their mineralized structure. This provides rigidity
to skeletal frames.
Muscle - Elastic fibers, collagens and glycoproteins within muscle ECM transmit
contractile forces between myofibrils and allow repetitive stretching and
contraction during movement.
Vasculature - Elastin within arteries and veins enables them to expand and
recoil with each heartbeat, regulating blood flow and pressure. Endothelial
basement membrane maintains vessel wall integrity.
Skin - Collagen fibrils layer the epidermis and dermis, providing tensile
strength and elastic recoil to withstand abrasion and pressure. Fibronectin
helps bind dermal fibroblasts during wound healing.
Lungs - Collagen and elastic fibers comprise the alveolar walls that must
inflate and deflate over 60,000 times daily for gas exchange. ECM elasticity
allows for repeated lung expansion.
Diseases Associated with Extracellular
Matrix Abnormalities
Defects in ECM structure or function underlie many diseases:
- Connective tissue disorders like Marfan syndrome and Ehlers-Danlos syndrome
arise from genetic defects in collagens and other matrix proteins, weakening
tendons, blood vessels and joints.
- Skin aging is due to decreased collagen synthesis and increased breakdown by
matrix metalloproteinases as we advance in age, causing wrinkles and sagging.
- Pulmonary fibrosis occurs when excess collagens accumulated amid lung tissue,
stiffening walls and impairing oxygen exchange.
- Heart disease risk is elevated with abnormalities in elastic fiber deposition
in arterial walls, predisposing to atherosclerosis.
- Cancer cell metastasis relies on secretion of proteinases to invade through
basement membrane barriers and migrate to distant sites.
- Wound healing is impaired when matrix production or remodeling is
dysregulated during inflammation and tissue regeneration phases.
Therapies Targeting Extracellular Matrix
Due to the central roles of ECM in health and disease, new therapies are
targeting this compartment:
- Collagen supplements are used cosmetically or to treat osteoporosis and
fibrosis by increasing structural proteins.
- Botulinum toxin injections block muscle ECM degradation in wrinkles by
inhibiting metalloproteinases.
- Anti-fibrotic drugs inhibit collagen synthesis for lung diseases like
idiopathic pulmonary fibrosis.
- Drugs preventing integrin-ECM interactions in cancer aim to block tumor cell
migration and angiogenesis.
- Growth factor supplements promote wound healing by stimulating new ECM
formation during injury repair.
ECM provides indispensable scaffolding and signals regulating tissue
architecture and homeostasis. Understanding its composition and dynamic
regulation promises to yield novel strategies for regenerative medicine,
anti-aging and disease treatment.
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