Lecture 7 - Healing 1 Flashcards
Which process is vital for resolution and healing?
Turning off of acute inflammation
Removal of the injurious stimulus
Describe the various cell populations in normal homeostasis
- Stem cells
- Baseline cell population
- Proliferating cells
- Differentiated cells
- Apoptotic cells
How do cells know whether to proliferate or undergo apoptosis?
Signalling
• Autocrine
• Paracrine
• Endocrine
What are the different groups of cells in terms of proliferative capacity?
- Labile cells
- Stable cells
- Permanent
What are stable cells?
Give some examples
- In G0 phase
- Can re-enter the cell cycle when exposed to particular stimuli
For example:
• Liver
• Pancreas
• Kidney
What are permanent cells?
Give some examples
Non dividing, can never re-enter the cell cycle
eg.
• Neurons
• Myocardium
What are labile cells?
Give some examples
Constantly dividing
• Epithelia
What does regeneration require?
What does replacement require?
Regeneration:
• Basement membrane
• Extracellular matrix interaction
Replacement:
• ECM interaction
Which cell types are important in healing?
- Fibroblasts
- Endothelial cells
- Epithelial cells
- Osteoblasts
Which ligands are important in proliferation?
- Growth factors
- Maxtrix proteins
- Cytokines
- Hormones
- Chemokines
Which receptors are important in proliferation?
- Receptor tyrosine kinases
- GPCR
- Cytokine receptors
Why is balance between stimulatory and inhibitory signals in proliferation important?
Stimulatory required to ‘re-awaken’ cells
However, inhibitory needed to prevent excessive proliferation and cancer
How do receptors without intrinsic catalytic activity function?
Which receptors don’t have intrinsic catalytic function?
They interact with a second messenger which does have catalytic activity
Cytokine receptors don’t have intrinsic catalytic activity
Which ligands commonly bind to GPCRs?
- Chemokines
* Hormones
What is the structure of GPCRs?
7 transmembrane domains
Describe the activity of RTKs
- Ligand (often GFs) binds
- Dimerisation
- Auto-phosphorylation at tyrosine residues
- Activation of tyrosine kinase activity
- Activation of adaptor molecules
→ Proliferation
Which general processes are brought about by growth factors?
- Proliferation
- Cell migration
- Promotion of cell survival
To which receptors do GFs mostly bind?
Receptor tyrosine kinases
Describe an example of proliferation without GFs
- Once cells fill out a space, they sense this and stop proliferating
- Some cells are removed → loss of cell-cell contacts
- Proliferation triggered
What is EGF?
Epithelial GF
• mitogenic for epithelial cells and fibroblasts
What is FGF?
Fibroblast GF
• angiogenesis
What is HGF?
Hepatocyte GF
• mitogenic for epithelial cells
What is VEGF?
Vascular endothelial GF
• vital for growth and proliferation of blood vessels
Which major pathways are involved in growth and proliferation?
- MAPK
- cAMP
- JAK / STAT