Fibrous extracellular matrix proteins Flashcards
What are examples of connective tissue?
- Blood
- Bone
- Tendon
- Skin
- Ligament
What pathological conditions are associated with abnormalities of the extracellular matrix?
- Arthritis
- Osteoporosis
- Cancer
- Diabetes
- Ageing
- Scars/fibrosis
What are 2 important fibrous proteins that make up the extracellular matrix?
Collagen + elastin
How are the collagen fibrils arranged in:
- tendons/ligaments
- bone
- cartilage
- tendons/lig - parallel bundles
- bone - spirals
- cartilage - meshwork
How many alpha chains are there in collagen forming the helix?
3 a chains - triple helix
Triple helices cross-link to form a FIBRIL
Each a chain is typically 3 amino acid repeats, what are they?
Glycine - proline - hydoxyproline
(Glycine ALWAYS as it acts as the glue, the other two are usual but not always)
Describe the pathway for synthesis of fibril-forming collagens
- Pro-alpha chains modified in ER
- Triple helix formed -> procollagen
- (extracellular) Procollagen secreted
- Propeptides cleaved -> collagen
- Striated + strength
How many known alpha chains are there for collagen structure?
25 known a-chains, >10,000 possibilities but only 20 types of collagen molecules found
What are the 3 most important collagen types?
I, II, III
Where is collagen type I found?
Bone
Where is collagen type III found?
Woven bone (not as strong as type I)
Where is collagen type II found?
Hyaline cartilage
What is the difference between a collagen fibril and fibre?
- Collagen molecule = 3 alpha chains forming a triple helix
- Collagen fibril = lots of overlapping molecules
- Collagen fibre = lots and lots of fibrils
Collagen types I and III are fibrillar collagens. There is another type called sheet-like collagens, how are they different + give an example?
- Type IV - in skin
- Lack regular glycine -> loose helix -> inc flexibility
- -> Sensitivity to digestion with proteases (so easily destroyed)
- Terminal peptides not cleaved
- Assemble head-to-head, form a sheet
What substances help to increase synthesis of extracellular matrix?
- TGF-beta (transforming growth factor-beta)
- PDGF (platelet derived growth factor)
What decreases synthesis of extracellular matrix?
- Glucocorticoids
- Age
What substances increase degradation of extracellular matrix?
MMPs (matrix metalloproteinases)
What substances decrease degradation of extracellular matrix?
TIMPs - tissue inhibitors of MMPS
What does collagenase (MMP1) destroy?
Native fibrillar collagens (type I, III etc)
What does gelatinase (MMP2/9) destroy?
- Denatured collagens
- Elastin
- Type IV (sheet like) collagen
What does stromelysin (MMP3) destroy?
- Type IV collagen
- Fibronectin
- Proteoglycans
Which proteolytic enzyme is involved in bone resorption?
Cathepsin K
What happens in scurvy?
- Loss of collagen
- Loss of glycine -> forms sheet-like collagen instead
- peridontal ligament (in teeth) broken down -> teeth fall out
There is a type 1 collagen mutation in osteogenesis imperfecta. What is glycine replaced with?
Cysteine -> disrupts alpha helix
What happens in achondrogenesis?
Type II collagen mutation - severe effects on development of cartilage and bone
What happens in Ehlers-danlos syndromes?
Type III or V collagent mutation - joint hyper mobility, skin extensibility, rupture of blood vessels
Elastin core is covered by sheath of microfibrils. The microfibrils are composed of which glycoprotein namely?
Fibrillin
The microfibrils are essential for integrity of elastic fibres
Does elastase increase or decrease synthesis of elastin? What inhibits elastase?
Decrease - it is inhibited by a1-anti-trypsin
What happens to elastin synthesis in hypertension?
Increased synthesis and deposition of elastin and collagen in vessel walls - they become thickened and diameter becomes reduced.
The turnover of elastin + collagen is slow, so difficult to treat.
What happens to elastin in pulmonary emphysema?
Loss of elastin = reduced elasticity of the lungs, sometimes due to deficiency of a1-anti-trypsin - needed to inhibit elastase.
So too much elastase = excessive degradation.
What is cutis laxa?
Loss of elastin - makes skin appear wrinkly
What is Marfan syndrome?
Mutation in fibrillin gene -> arachnodactyly, pectus excavatum, dilation of aorta
