Lecture 8 - Healing 2 Flashcards
What is the structure of proteoglycans?
Name an important proteoglycan
Core protein + glycosaminoglycans
Draw this
• Many -ve charges
Aggrecan
What is the function of cadherins?
Adherence of two neighbouring cells of the same type
What happens when cells aren’t bound by integrins?
Apoptosis is triggered
Describe the function of proteoglycans
• Hold a lot of water, forming a gel-like structure
• Reservoir for GFs (bind GFs on their G3 region)
→ Modulate cell growth and differentiation
What are the essential processes in healing?
Describe briefly which factors mediate these processes
- Angiogenesis
• EPCs: endothelial precursor cells
• VEGF - Fibroplasia
• Fibroblasts - Remodelling
Describe angiogenesis
‘Explosion’ of new blood vessels
– Proliferation from existing vasculature –
- VEGF binds to VEGFR on endothelium
- Endothelial cells re-enter cell cycle
- Sprouting of capillaries
- Reorganisation, maturation
– Proliferation from EPCs from BM –
- VEGF released from ECM stimulated EPCs in BM
- EPCs migrate to vasculature
- EPCs start to proliferate
- New branches made
- Stabilisation of vessels:
• Pericytes
• Smooth muscle
• Connective tissue
What is vasculogenesis?
Describe the process
Specialised form of angiogenesis during embryogenesis
Laid down for the first time
What is fibroplasia?
Compare this with fibrosis
Formation of new connective tissue
Fibrosis is any abnormal laying down of connective tissue
What is remodelling?
Maturation and reorganisation of fibrous tissue
Vascular granulation tissue → avascular scar
Which stem cells give rise to new vasculature?
EPCs
Endothelial precursor cells
Where does VEGF come from?
When is it induced?
ECM cells Indued by: • Hypoxia • TGF-β • PDGF
How is angiogenesis controlled?
Interactions between: • GFs • Vascular cells • ECM Stabilisation of vessels
Describe stabilisation of new vasculature and how this is initiated
Must be stabilised
• Pericytes
• ECM
• Smooth muscle
Initiated by:
• Angiopoietin
• PDGF
• TGF-β
Which cytokine plays a central role in fibroplasia?
TGF-β
What is the role of macrophages in fibroplasia?
- Clear debris
* Secrete GFs
What happens to vasculature as the scar matures?
Vascular regression
Compare healing of small and large wounds
Small:
1. Scab formation, neutrophil infiltrate
2. Regeneration of epithelium
NB Minimal inflammation
Large 1. Big scab 2. Fibrosis, replacement of tissue 3. Scar formation NB Inflammation
What is the definition of ECM?
- Macromolecules outside cells
- Formed by local secretion
- Assembled into network surrounding cells
What are the general functions of the ECM?
- Reservoir for GFs
- Reservoir for water
- Scaffold
What is the basement membrane?
Describe its structure
Specialised part of the ECM
Structure:
• Laminin
• Proteoglycan
• Collagen type IV
What are the two groups of matrix components?
- Basement membrane
* Interstitial matrix
What are the three types of molecules found in ECM?
- Fibrous proteins
- Adhesive proteins
- Gelatinous-like molecules
What are some examples of fibrous proteins?
- Collagen
* Elastin
What are some examples of adhesion proteins?
- Fibronectin
* Laminin
What are some examples of gelatinous-like molecules?
- Proteoglycan
* Hyaluronan
Why is collagen important in terms of abundance?
Most common protein in the animal world