Lecture 33

Question 1

Differentiate tissue regeneration and tissue repair.

Answer 1

regeneration: replacement of injured tissue with cells of the same type and function

repair: occurs when extent or nature of damage cannot be reversed by regeneration; doesn’t go back to its normal state

Question 2

State the four stages of healing after tissue injury.

Answer 2

1. Hemostasis- minutes; results in local vasoconstriction and activation of platelets and clotting factors to form a fibrin clot. This creates the scaffold for migrating cells.
2. Inflammation- hours; driven by platelet-derived mediators, bacteria, and secreted chemoattractants.
3. Proliferation- days; mediated by macrophage and fibroblast-mediated growth factors.
4. Remodeling- weeks to months; transition from type III to type I collagen, restoring tensile strength of tissue.

Question 3

Identify the determinants of regeneration versus repair after tissue injury.

Answer 3

1. Nature of cells injured- some cells (e.g. adult cardiac myocytes) have marginal renewal capacity
2. Extent of injury- the magnitude of the injury may exceed regeneration capacity
3. Presence or absence of ongoing inflammation- due to concurrent infection or other factors, continued release of inflammatory mediators may disrupt balance toward repair
4. Underlying disease- may impair proliferative response or remodeling (e.g. diabetes)

Question 4

State the outcome of various signal transduction pathways of growth factors.

Answer 4

transcription factor activation and change in gene expression:
PI3 kinase pathway
MAP-kinase pathway
IP3 pathway
cAMP pathway
JAK/STAT pathway

epidermal growth factor (EGF):
- transcription factor activation and change in gene expression
- activation of a protein kinase cascade
- source: activated macrophages, keratinocytes, and many other cells
- function: mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte migration and granulation tissue formation

Question 5

Describe the two forms of ECM and their key components.

Answer 5

basement membrane:
- type IV collagen
- laminin
- proteoglycan

interstitial matrix:
- fibrillar collagens
- elastin
- proteoglycan and hyaluronan

Question 6

Identify the three key growth factors that regulate fibrosis.

Answer 6

1. PDGF (platelet-derived growth factor):
   - migration and proliferation of fibroblasts, smooth muscle cells, and macrophages
2. TGFβ (transforming growth factor):
   - potent fibrinogenic factor that stimulates collagen, fibronectin, and proteoglycan synthesis
   - inhibits collagen degradation
   - inhibits lymphocyte proliferation
   - has anti-inflammatory effect
3. FGF-2 (fibroblast growth factor):
   - stimulated proliferation of endothelial cells
   - promotes migration of macrophages and fibroblasts to damaged areas