L9: Extracellular Matrix Flashcards

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1
Q

Functional attributes of ECM

A
  1. Structure
  2. Defense/protection/barrier
  3. Nutrition (diffusion of metabolic fuels)
  4. Diffusion of gases, molecules and ions
  5. Cell growth and survival
  6. Cell migration
  7. Lubrication
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2
Q

What is granulation tissue?

A
  • Tissue that is the hallmark of tissue repair
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3
Q

Basic structures of the ECM

A
  1. ) Ground substance
    - Glycosaminoglycans/mucopolysaccharides
    - Proteoglycans
    - Multiadhesive Glycoproteins
    - Water
  2. ) Fibers/CT
    - Collagen
    - Reticular (type III collagen)
    - Elastic
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4
Q

Characteristics of ground substance. Function

A

Characteristics:
- Amorphous intercellular material that is transparent, colorless and homogenous, hydrated, fills space b/w cells and fibers, viscous
Function:
- Acts as lubricant, barrier and provides structure, diffusion medium for metabolites

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5
Q

What are the molecules that make up ground substance?

A
  • Glycosaminoglycans/mucopolysaccharides
  • Proteoglycans
  • Multiadhesive Glycoproteins
  • Water
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6
Q

Structure and function of glycosaminoglycans

A
  • Linear polymers of disaccharides that have negatively charged carbosyl groups that attract cations, which attract extracellular fluid. Function here = hydrating effect, which allows for compression resistance
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7
Q

Clinical relevance of glycosaminoglycans

A
  • In Grave’s disease, increased deposition of GAGs (hyaluronic acid and chondroitin sulfate) in retroorbital space that causes exophthalmos.
  • Excess deposition of GAGs in Grave’s also involves skin
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8
Q

List of glycosaminoglycans

A
  1. ) Dermatan sulfate
  2. ) Chondroitin sulfate
  3. ) Heparan sulfate
  4. ) Keratan sulfate
  5. ) Hyaluronic acid
  6. ) Heparin
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9
Q

Structure of proteoglycans

A
  • Linear chains of glycosaminoglycans bound to protein core, majority of weight is attributable to CHOs
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10
Q

Types of proteoglycans

A
  1. ) Syndecan
  2. ) Perlecan
  3. ) Decorin
  4. ) Versican
  5. ) Aggrecan
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11
Q

What is syndecan? Function?

A
  • Syndecan is a type of proteoglycan where core protein of molecule is embedded in cell membrane as transmembrane protein
  • In fibroblasts, syndecan serves as co-receptor for fibroblast growth factor
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12
Q

What is perlecan? Function?

A
  • Major proteoglycan type found in basement membranes and CT

- Function = cell adhesion, proliferation, glomerular filtration, development and growth factor binding

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13
Q

Clinical relevance of perlecan

A
  • Enhanced in some types of tumors, promoting proliferation and angiogenesis
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14
Q

Function of versican

A
  • Important in cell-cell and cell-ECM interactions
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15
Q

What are multiadhesive glycoproteins?

A
  • Glycoproteins that molecularly tether cell to EC elements
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16
Q

Structure of multiadhesive glycoproteins?

A
  • Have three primary binding sites:
  • 1.) one for integrins (cell adhesion molecules)
  • 2.) one for collagen fibers
  • 3.) one for proteoglycans
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17
Q

List types of glycoproteins

A
  1. ) Fibronectin
  2. ) Laminin
  3. ) Nidogen (entactin)
  4. ) Tenascin
  5. ) Chrondronectin
  6. ) Osteonectin
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18
Q

List types of glycoproteins. What are their binding domains and where are they located?

A

1.) Fibronectin
Binding domains: integrins, collagen, heparin, heparan sulfate and hyaluronic acid
Location: CT, blood plasma, embryonic tissue

2.) Laminin
Binding domains: integrins, heparan sulfate, collagen (IV) and entactin
Location: basal lamina

3.) Nidogen (entactin)
Binding domains: laminin and type IV collagen
Location: basal lamina

4.) Tenascin
Binding domains: syndecans and fibronectin
Location: embryonic tissue

5.) Chrondronectin
Binding domains: collagen II, chondroitin sulfates, hyaluronic acid and integrins of chrondrocytes
Location: cartilage

6.) Osteonectin
Binding domains: collagen I, proteoglycans, integrins of bone cells (cytes and blasts)
Location: bone

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19
Q

List fibers of ECM

A
  1. ) Collagen
  2. ) Reticular
  3. ) Elastic
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20
Q

What is the most abundant protein in the body?

A
  • Collagen (20-25% of all protein), specifically type I
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21
Q

Principle amino acids that make up collagen?

A
  • Principly glycine (every 3rd AA)

- Also hydroxyproline and hydroxylysine (both specific to collagen)

22
Q

Type I Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: dermis, tendon, bone, dentin, cementum, fibrocartilage, organ capsules
  2. Synthesizing cells: fibroblasts, odontoblasts, cementoblasts, osteoblasts, chondroblasts
  3. Function: resistance to tension
  4. Organization: fibril-forming
23
Q

Type II Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: hyaline and elastic cartilage
  2. Synthesizing cells: chondroblasts
  3. Function: resistance to pressure
  4. Organization: fibril-forming
24
Q

Type III Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: spleen, liver, lymph nodes, smooth muscle, skin, lung
  2. Synthesizing cells: smooth muscle cells, fibroblasts, reticular cells
  3. Function: maintains structure in expansible organs
  4. Organization: fibril-forming
25
Q

Type IV Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: basal lamina
  2. Synthesizing cells: endothelial cells, epithelial cells, Schwann cells and smooth muscle cells
  3. Function: support of delicate structures and filtration
  4. Organization: network-forming
26
Q

Type V Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: dermis, tendon, bone, fibrocartilage
  2. Synthesizing cells: fibroblasts, mesenchymal cells
  3. Function: participates in type I collagen function
  4. Organization: fibril-forming
27
Q

Type VII Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: dermis
  2. Synthesizing cells: epidermal cells
  3. Function: anchors lamina densa to lamina reticularis
  4. Organization: anchoring
28
Q

Type IX Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: hyaline cartilage
  2. Synthesizing cells: chondroblasts
  3. Function: binds collagen fibrils to one another
  4. Organization: fibril-associated
29
Q

Type XI Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: hyaline cartilage
  2. Synthesizing cells: chondroblasts
  3. Function: participates in type II function
  4. Organization: fibril-forming
30
Q

Type XII Collagen. Tissue distribution, synthesizing cells, function, organization?

A
  1. Tissue distribution: tendons, ligaments
  2. Synthesizing cells: fibroblasts
  3. Function: binds collagen fibrils to one another
  4. Organization: fibril-associated
31
Q

What happens to the hydrated state of tissue where there is excessive accumulation of GAGs? No change, decrease and increase?

A
  • Increase
32
Q

What does inactivation of the gene for perlecan result in?

A
  • Defective skeletal development
33
Q

What amino acid is measured to calculate the concentration of collagen?

A
  • Hydroxyproline or hydroxylysine, both which are specific to collagen
  • Glycine is principle AA in collagen, but not specific for it
34
Q

What are reticular fibers?

A
  • Reticular fiber are composed of type III collagen
35
Q

What chemical is used to stain reticular fibers?

A
  • Silver (argyrophilic) and PAS (magenta color)
36
Q

What cell types synthesize reticular fibers? In what tissues are reticular fibers found?

A
  • Fibrocytes, reticulocytes, smooth myocytes and Schwann cells
  • Tissues: spleen, liver, lymph nodes, smooth muscle, skin and lung
37
Q

Elastic fibers. Function, attributes/characteristics, synthesizing cells, molecular composition

A
  1. ) Function: imparts tissue with elasticity
  2. ) Attributes: slender and branched, densely arranged in bundles, nonfibrous elastic tissue arranged in fenestrated sheets (blood vessels), turnover is poor
  3. ) Synthesizing cells: fibroblasts, smooth muscle cells, chondroblasts
  4. ) Molecular composition: three components needed to form elastic fibers: a.) proelastin (tropoelastin = cleaved form), b.) microfibril-associated glycoprotein and c.) fibrillin (1&2)
38
Q

Discuss unique findings of proelastin

A
  • Proelastin is a component of elastic fibers

- Contains unique amino acids desmosine and isodesmosine

39
Q

Discuss Ehlers-Danlos types IV, VI and VII. What is the defect and what are the clinical consequences?

A
  1. ) Type IV
    - Defect: mutation in Col3A1 gene encoding type III collagen (aka reticular fibers)
    - Clinical: varicose veins, aortic rupture, intestinal rupture
  2. ) Type VI
    - Defect: defective hydroxylation of lysine destabilizes strength of collagen
    - Clinical: hyperelasticity of skin, rupture of eyeball
  3. ) Type VII
    - Defect: mutations in Col1A1 and Col1A2 genes encoding type I collagen
    - Clinical: joint dislocation and hypermobility of joints
40
Q

Scurvy. Defect and clinical consequences?

A
  • Defect: tropocollagen molecules cannot aggregate into fibrils due to decreased hydroxylation of proline caused by deficiency in vitamin C
  • Clinical: gum ulceration and hemorrhages
41
Q

Osteogenesis imperfecta. Defect and clinical consequences?

A
  • Defect: mutations in Col1A1 leads to reduction in the synthesis of type I collagen
  • Clinical: spontaneous fractures and cardiac insufficiency
42
Q

Strickler syndrome. Defect and clinical consequences?

A
  • Defect: mutation in Col2A1 gene encoding for type II collagen
  • Clinical: myopia (near-sighted), hypoplasia of mandible, arthritis
43
Q

Marfan syndrome. Defect and clinical consequences?

A
  • Defect: mutation of the fibrillin 1 gene on c/s 15
  • Clinical: aortic aneurysm or rupture, myopia (near-sighted), detached lens, skeletal defects: long thin arms, legs, toes, fingers, pectus excavatum, scoliosis
44
Q

What stains elastic fibers?

A
  • Resorcin-fuchsin or Verhoeff stains (black)
45
Q

Discuss difference between the basal lamina and basement membrane. What is the composition?

A
  1. ) Lamina lucida: composed of laminin, entactin, integrins and dystroglycans (integrins and dystroglycans are transmembrane receptors for laminin)
  2. ) Lamina densa: composed of type IV collagen, fibronectin and perlecan
  3. ) Lamina fibroreticularis: composed of fibronectin and types I and II collagen
  • Basal lamina = lamina lucida + lamina densa
  • Basement membrane = basal lamina + lamina fibroreticularis
46
Q

What anchors the basal lamina to the lamina fibroreticularis?

A
  • Anchoring fibrils of type VII collagen, fibrilin and fibronectin
47
Q

Function of basal lamina and basement membrane?

A
  • Adhesion interface bw epithelium and ECM, molecular filter, regulation of cell differentiation, proliferation, organization and regeneration of cells
48
Q

What is basal lamina associated with non-epithelial cells called?

A
  • non-epithelial: muscle, adipocytes and Schwann cells

- called external lamina

49
Q

Clinical relevance of basal lamina and basement membrane?

A
  • Basal lamina prevents spread of epithelial tumors unless broken down
  • Goodpasture Syndrome = autoimmune dz in which antibodies develop against specific type IV collagen subunit
  • Developmental failure demonstrated in mouse model if laminin is defective or has deficit
50
Q

What are keloids?

A
  • Excessive deposition of collage in scar formation
51
Q

Excessive deposition of collagen

A
  • MI

- Keloid/scar formation

52
Q

A 38 yo male presents with fatigue and edema. Lab studies reveal urine sediments, urine protein, primary albumin. Biopsy of kidney was obtained and sent to pathology. Membranous nephropathy seen: Prominent spikes of silver-staining matrix projecting from basement membrane lamina densa toward urinary space, which separate and surround deposited immune complexes that lack affinity for silver stain. Electron micrograph shows electron-dense deposits along epithelial side of basement membrane. What is the diagnosis?

A
  • Goodpasture’s Syndrome: autoimmune dz in which antibodies develop against specific type IV collagen subunit.
  • Leakier kidneys