Extracellular matrix in the best

1. EXTRACELLULAR MATRIX
• Components and functions
• Role of ECM in health and disease

2. AGENDA
◎ What is extracellular matrix?
◎ Composition of ECM
◎ Functions of ECM
◎ Associated diseases
◎ Summary
◎ Approximate time: 35 – 40 minutes
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6. Cells Tissues Organs Systems
CONNECTIVE TISSUE? EXTRACELLULAR MATRIX

7. Substantial part of tissue volume: Extracellular space
largely filled by macromolecules of ECM
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Generally secreted by cells of the tissue
Assembled into a meshwork
Different
functions in
different
tissues

8. Different cells have different proportions of cellular and
extracellular components
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Epithelial cells:
More cellular
components,
less ECM
Connective tissue:
Less cellular
components, more
ECM
Physical
characteristics
different:
Blood is
liquid,
collagen is
spongy

9. ECM IS MADE OF THREE COMPONENTS
ECM
Glycans
Glycosaminoglycans
Proteoglycans
Fibrous proteins
Collagen
Elastin
Adhesive proteins
Fibronectin
Laminin
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10. PROTEOGLYCANS
◎ Aggregates of GAGs (mucopolysaccharides) and
proteins (chondroitin sulphate most common)
○ Negative charge, repel each other (slippery)
○ Water fills the ECM, repels the forces of tissue
compression (resists compression)
○ GAG + collagen in cartilage of big joints (water
squeezed out during compression, once the pressure is released,
water rushes back) - Resilience
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11. FIBROUS PROTEINS
◎ Structural components (secondary structure)
◎ Collagen and Elastin
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• Most abundant protein
• Main protein in bone,
skin, and tendon
• ECM as a gel like
substance, provides
support and strength
• 28 different types
(90% is type 1 to 4)
• Mainly seen in skin, arteries, and
lungs
• Contains less hydroxyproline than
collagen
• No carbohydrates in elastin

12. CELL ADHESION MOLECULES
◎ Cell to cell and cell to ECM adhesions mediated by
plasma membrane anchored proteins (cell adhesion molecules)
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Forms junctions:
• Tight/occluding
• Anchoring/desmosomes
• Gap/communicating
Transmembrane proteins
• Extend from cytoplasm through
plasma membrane into EC space
• Binds to specific ligands
• Cadherins
• Selectins
• Immunoglobulin superfamily
• Integrins
• Holds cells together,
maintains cell integrity
• Needs calcium
Important in WBC
migration to sites of
inflammation
• Structural similarity to
immunoglobulins
• May be involved in
immunological functions
Cell to cell and cell to
ECM adhesions
Weaker interaction

13. DISEASES ASSOCIATED WITH FIBROUS PROTEINS
◎ Scurvy
◎ Osteogenesis imperfecta
◎ Ehlers – Danlos syndrome
◎ Marfan syndrome
◎ α1 Antitrypsin deficiency
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14. SCURVY
◎ Deficiency of Vitamin C
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Impaired hydroxylation of
proline and lysine
Defective pro-α chains
Lack of stable triple helix
Less normal functional
collagen
Fragile blood vessels
Slow wound healing
Gingival bleeding
Tooth loss
ACQUIRED

15. OSTEOGENESIS IMPERFECTA
◎ Brittle bone disease
◎ Any of the many mutations in collagen gene
◎ Currently, eight subtypes identified
◎ Most common is Type 1, most lethal is Type 2
◎ Most are AD
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INHERITED

16. EHLERS DANLOS SYNDROME
◎ Uncommon
◎ Inherited defects in the structure, production, or
processing of collagen
◎ Six major types, all affects joints and skin
◎ Most are AD
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17. MARFAN SYNDROME
◎ Mutation in the gene coding for Fibrillin -1
(component of elastin)
◎ Most affected organs
◎ Long limbs and digits
◎ Tall stature
◎ Scoliosis
◎ Myopia, astigmatism
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18. α1 ANTITRYPSIN DEFICIENCY
◎ Elastin is involved (like Marfan)
◎ Inappropriate destruction of lung
elastin by elastase
◎ Manifests as emphysema
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Elastase
α1 Antitrypsin

19. CELL ADHESION AND DISEASE
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REDUCED ADHESION INCREASED ADHESION
Cancers
Leukocyte adhesion
defects
Pemphigus
Asthma
Rheumatoid arthritis
As receptor
for viruses
CAUSES DISEASES
Fatty streak in
atherosclerosis