Extracellular matrix Flashcards
What are the basic elements of the ECM?
1) Ground substance
2) Fibers
3) Granulation tissue
What are the characteristics of the ground substance?
1) Amorphous intercellular material
2) Hydrated
3) Fills space between cells and fibers
4) Viscous
5) Acts as lubricant, barrier, and provides structure
6) Diffusion medium for metabolites, O2, CO2, growth factors
What are the molecular moieties of the ground substance?
1) Glycosaminoglycans
2) Proteoglycans
3) Multiadhesive glycoproteins
4) Water
What are glycosaminoglycans comprised of?
Linear polymers of disaccharides
How is the hydrating effect of glycoasminoglycans accomplished?
Negative carboxyl groups attract cations, which attracts extracellular fluid
In Grave’s disease, which extracellular matrix component is increased?
Glycosaminoglycans (e.g. hyaluronic acid, chondroitin sulfate)
What is another term for glycosaminoglycans?
Mucopolysaccharides
What are proteoglycans composed of?
Linear chains of glycosaminoglycans bound to a protein core
Linear chains of glycosaminoglycans bound to a protein core constitute what extracellular matrix component?
Proteoglycans
What is an aggrecan?
Proteoglycans non-covalently linked to hyaluronic acid
What is the term for proteoglycans non-covalently linked to hyaluronic acid?
Aggrecans
What is a syndecan?
Transmembrane proteoglycan
What type of proteoglycan serves as a co-receptor for fibroblast growth factor?
Syndecan
Syndecan serves as a co-receptor for what growth factor?
Fibroblast growth factor
What is the major proteoglycan found in the basement membrane and connective tissues?
Perlecan
What is the function of perlecan?
1) Cell adhesion
2) Proliferation
3) Differentiation
4) Glomerular filtration
5) Development
6) Growth factor binding
How does gene inactivation for perlecan affect skeletal development?
Impairs skeletal development
What is the importance of versican?
Cell-to-cell and cell-to-ECM interactions
What are multiadhesive glycoproteins?
Glycoproteins that molecularly tether the cell to extracellular elements
Which glycoproteins molecularly tether the cell to extracellular elements?
Multiadhesive glycoproteins
What are the three binding sites for multiadhesive glycoproteins?
1) One for integrins
2) One for collagen fibers
3) One for proteoglycans
Where is fibronectin found?
1) Connective tissue
2) Blood plasma
3) Embryonic tissue
Where is laminin found?
Basal lamina
Where is nidogen (enactin) found?
Basal lamina
Where is tenascin found?
Embryonic tissue
Where is chondronectin found?
Cartilage
Where is osteonectin found?
Bone
Collagen is primarily made up of what amino acids?
1) Glycine
2) Hydroxyproline
3) Hydroxylysine
What is the most abundant collagen type?
Type I
What is the tissue distribution of type I collagen?
1) Dermis
2) Tendon
3) Bone
4) Dentin
5) Cementum
6) Fibrocartilage
7) Organ capsules
What is the function of type I collagen?
Resistance to tension
What is the tissue distribution of type II collagen?
Hyaline and elastic cartilage
What is the function of type II collagen?
Resistance to pressure
What is the tissue distribution of type III collagen?
1) Spleen
2) Liver
3) Lymph nodes
4) Smooth muscle
5) Skin
6) Lungs
What is the function of type III collagen?
Maintains structure in expandable organs
What is the tissue distribution of type IV collagen?
Basal lamina
What is the function of type IV collagen?
Support of delicate structures and filtration
What is the tissue distribution of type V collagen?
Dermis
What is the function of type VII collagen?
Anchors the basal lamina to the lamina reticularis
Reticular fibers are composed of what type of collagen?
Type III
What stains could be used to detect reticular fibers?
1) Silver Methods
2) PAS Reaction
What are the attributes of elastic fibers?
1) Slender and branched (loose CT)
2) Densely arranged in bundles (ligamentum flavum)
3) Detected by resorcin-fuschin or Verhoeff
What stains detect elastic fibers?
1) Resorcin-fuschin
2) Verhoeff
How is nonfibrous elastic tissue arranged?
Fenestrated sheets or lamellae
Which cells synthesize elastic fibers?
1) Fibroblasts
2) Smooth muscle cells
3) Chondroblasts
Which three components must be synthesized to form elastic fibers?
1) Proelastin
2) Microfibril-associated glycoprotein
3) Fibrillin (1 and 2)
What is the defect associated with EDS IV?
Mutation in COL3A1 gene encoding type III collagen (reticular fibers)
What are the clinical consequences of EDS IV?
1) Varicose veins
2) Aortic rupture
3) Intestinal rupture
What is the defect associated with EDS VI?
Defective hydroxylation of lysine - destabilizes collagen strength
What are the clinical consequences of EDS VI?
1) Hyperelasticity of the skin
2) Rupture of the eyeball
What is the defect associated with EDS VII?
Mutations of the COL1A1 and COL1A2 genes encoding type I collagen
What are the clinical consequences of EDS VII?
1) Joint dislocation
2) Hypermobility of joints
What is the defect associated with scurvy?
Tropocollagen molecules cannot aggregate into fibrils due to decreased hydroxylation of proline caused by vitamin C deficiency
What are the clinical consequences of scurvy?
1) Gum ulceration
2) Hemorrhages
What is the defect associated with osteogenesis imperfecta?
Mutations in the COL1A1 gene leading to reduction in type I collagen production
What are the clinical consequences of osteogenesis imeprfecta?
1) Spontaneous fractures
2) Cardiac insufficiency
What is the defect associated with Strickler syndrome?
Mutation in COL2A1 gene encoding for type II collagen
What are the clinical consequences of Strickler syndrome?
1) Myopia
2) Hypoplasia of mandible
3) Arthritis
What is the defect associated with Marfan syndrome?
Mutation of fibrillin 1 gene on chromosome 15
What are the clinical consequences of Marfan syndrome?
1) Aortic aneurysm or rupture
2) Myopia
3) Detached lens
4) Skeletal defects
5) Pectus excavatum
6) Scoliosis
What makes up the basal lamina?
Lamina lucida (variable) + lamina densa
What part of the basal lamina is secreted by epithelial, muscle, adipose, and Schwann cells?
Lamina densa
What makes up the basal membrane?
Basal lamina + lamina fibroreticularis
What part of the basal membrane is secreted by fibroblasts?
Lamina fibroreticularis
What makes up the lamina lucida?
1) Laminin
2) Entactin (nidogen)
3) Integrins
4) Dystroglycans
What are the transmembrane receptors for laminin?
1) Integrins
2) Dystroglycans
What is the lamina densa composed of?
1) Type IV collagen
2) Fibronectin
3) Perlecan
Type IV collagen, fibronectin, and perlecan make up what layer of the basal membrane?
Lamina densa
What is the lamina fibroreticularis composed of?
1) Fibronectin
2) Type I collagen
3) Type III collagen
How is the basal lamina anchored to lamina fibroreticularis?
Anchoring fibrils of :
1) Type VII collagen
2) Fibrillin
3) FIbronectin
The external lamina surrounds what elements?
Nonepithelial cells (muscle, adipocytes, Schwann cells)
Nonepithelial cells are surrounded by what type of basal lamina?
External lamina
What are the functions of the basement membrane?
1) Adhesion interface between epithelium and ECM
2) Molecular filter
3) Regulation of cell differentiation, proliferation, and organization
4) Regeneration of cells
In Goodpasture syndrome, antibodies are formed against what type of collagen?
Type IV collagen
Antibodies against type IV collagen are formed in what disease?
Goodpasture syndrome
