What are the two types of healing that can occur after an injury?
Regeneration (replacement of damaged cells with new cells) and repair (replacement of damaged cells with fibrous tissue).
Where are replacement cells for cell regeneration?
What are the three forms of chemical mediators that can signal cells to proliferate?
Autocrines (hormones secreted by the same cell), paracrines (hormones secreted by neighbouring cells) and endocrines (systemic hormones made in other organs).
What are the three states that a cell can be in with regards to cell regeneration?
The cell can be either mitotically active, stable or permanent.
What are mitotically active cells?
Cells that are mitotically active usually have very short life spans and always need to be replaced. These cells include skin and red blood cells.
what are stable cells?
Cells that are stable will only be replaced if they the old ones are damaged-otherwise they are fine. Cells like these have limited regenerative capacity and require the stroma to be intact. Examples would be the liver and kidney cells.
what are permanent cells?
Cells that are permanent have no capacity to regenerate when damaged. These cells can only be replaced with fibrous tissue, forming scars. Examples are neurons and cardiac myocytes.
What factors affect healing of an injury?
The cell state (active, stable and permanent) and the injury severity.
What is the main molecular mechanism that triggers cell proliferation during regeneration?
What is the molecular mechanism behind cell proliferation ?
Growth factors bind to the receptors, and the tyrosine kinase enzyme is self phosphorylated. The tyrosine kinases are activated, and they active other cytoplasmic proteins. Eventually, cell proliferation starts.
What are three important growth factors that trigger cell proliferation?
epithelial growth factor, Transforming growth factor and platelet derived growth factor.
what is the mechanism behind cell proliferation that occurs without growth factors?
Cells can be triggered to proliferate from increased pressure from neighbouring cells that are themselves proliferating.
What is a mitogen?
A chemical substance that binds to a cell and encourages it to undergo cell division/proliferation (undergo mitosis).
How does cell proliferation happen according to the MAP Kinase pathway?
The MAP kinase pathway involves a mitogenic ligand binding to its receptor on the cell membrane. Then the receptor becomes activated by phosphorylation. Many other cytoplasmic proteins are phosphorylated, including transcription factors, that will enable gene transcription.
what is the risk of this MAP kinase pathway with regards to cell replication?
There is a delicate balance between the transcription of too many oncogenes, which could lead to uncontrollable cell division. Thus, tumour suppressant genes must also be transcribed to equally inhibit cell division.
What is the pathological consequence of not controlling the cell cycle tightly?
Tumour growth (cancer).
Where are the two checkpoints for newly replicated DNA quality in the cell cycle?
There is the G2/M phase checkpoint, and the G1/S phase checkpoint.
What are the cyclins and what is their role in the cell cycle?
The cyclins regulate the individual steps of the cell cycle.
Can cells replicate without the extracellular matrix?
No-they need the extracellular matrix to replicate.
What are the two main matrix components?
Interstitial matrix: spaces between the cells, e.g stroma.
Basement membrane: It's not actually a membrane, its a matrix. It sits immediately below epithelial cell layers
What are the 3 groups of extracellular matrix components?
Fibrous proteins (collagens and elastins): They contribute to the physical structure of the matrix.
Adhesive glycoproteins (fibronectin, laminin): Holds matrix together
Gelatinous-like molecules (proteoglycans): Draws water into matrix for jelly-like consistency
What is the role of the fibrous protein group found in the matrix?
Collagen is the most prominent fibrous protein in the matrix.
The fibrillar kind is responsible for cartilage and so forth-not relevant to the matrix.
The non fibrillar kind is present in the matrix and forms sheets within the basement membrane (like a lasagna).
What is the role of the Fibrous group protein, Elastin?
Elastins form long elastic fibres that help structures in the body to stretch and recoil back into their shape without any damage.
What does fibronectin do as an adhesive glycoprotein in the extracellular matrix?
Fibronectin is an adhesive glycoprotein that is produced by fibroblasts.
It enables cell attachment and spreading, cell migration and enhances sensitivity to growth factors.
What is the role of cadherins family in the adhesive glycoproteins group within the extracellular matrix?
The Cadherins are proteins responsible for enabling cell adhesion. They enable the cell to produce and express the adherins necesary to undergo adhesion.
What does laminin do as a adhesive glycoprotein in the extracellular matrix?
It is the most abundant glycoprotein in the basement membrane.
It mediates cell attachment to connective tissue and binds to integrins.
What is the role of the gel-producing proteins family, the proteoglycans?
Proteoglycans have many negative charges on their molecules that attract cations salts and thus attract water. They store growth factors and modulate cell growth and differentiation.
What are the three essential processes in repair?
Angiogenesis, fibroplasia and remodelling.
How does angiogenesis work?
VEGF is the master growth factor responsible for angiogenesis. It binds to the VEGF receptor in the bone marrow, and triggers the release of the epithelial progenitor cells (EPC's). The EPC's travel to the site of vascular injury by haemotaxis. Once there, VEGF-2 organises them into new blood vessels.
How does fibroplasia work?
The fibroblasts are activated to proliferate by the healing chemokines and they produce fibrin to replace the dead, or damaged cells.
How does the extracellular matrix change during remodelling?
Initially, the new extracellular matrix is being made and so net synthesis occurs.
Whilst this is happening, matrix metalloproteinases degrade the excess ECM to make sure not too much collagen is laid down.
The balance of these leads to an even scar/granulation tissue being made.
How does healing occur in small wounds, or clean, surgical wounds?
Epithelial regeneration predominates over fibrosis.
Healing is fast, with minimal inflammation and scarring.
How does healing occur in large, unclean wounds?
Fibrosis predominates over epithelial regeneration.
Healing is slower, with more inflammation and granulation tissue/scarring made.
Permanent scars and not regeneration, because so much ECM is made that it cannot all be cleared.