Wound Repair Flashcards
What are some of the tissues that regenerate themselves due to normal “wear and tear”?
hematopoietic system, skin epithelium, and gastrointestinal epithelium
What are labile cells?
continuously dividing cells
Which phase of the cell cycle is the cell committed to replicate or die?
S
Which phase of the cycle has cells that aren’t actively dividing?
G0
What are cyclins?
molecules that bind to cdk to form a heterodimer that phosphorylates retnoblastoma, the main controller of the G1/S transition
What cell types reside in the G0 phase?
liver, kidneys, pancreas, mesenchymal cells, resting lymphocytes, and vascular endothelial cells
What are some examples of permanent cells?
neurons, cardiac myocytes and skeletal myocytes
What is the receptor for EGF and TGF-a?
EGFR1 (ERB B1)
What is the receptor for EGF?
tyrosine-specific kinase
T/F EGF acts in paracrine fashion
F. Juxtacrine
What are the cells of origin of EGF?
macrophages, inflammatory cells, and platelets
What are the target cells of EGF?
epithelial and fibroblasts
What is the main effect of EGF?
cell proliferation
What is the function of TGF-a and what pathology is associated with it?
facilitates regeneration of epithelium; psoriasis
What is KGF?
stimulates keratinocyte division and differentiation
What is the receptor for PDGF and what receptor type is it?
PDGFa and b and tyrosine-specific kinase
What are the cells of origin for PDGF?
macrophages, endothelial cells, platelet alpha granules and fibroblasts
What is PDGF’s target cell?
mesenchymal cells
What are some of the effects of PDGF?
1) chemokine for neutrophils, macrophages, and fibroblasts
2) mitogen (increases fibroblast proliferation)
3) stimulates fibroblasts to secrete ECM and collagenase
What are the cells of origin for FGFs
macrophages and endothelial cells
What are the target cells of FGFs?
fibroblasts and endothelial cells
T/F FGF must be bound to ECM (syndecane) in order to activate the receptor
True
What are some of the effects of FGF?
1) fibroblast chemotaxis and proliferation
2) ECM deposition
3) angiogenesis
What are the target cells of VEGF?
endothelial cells
What is the cell of origin for VEGF?
mesenchymal cells
What are some of the effects of VEGF?
1) angiogenesis
2) endothelial cell proliferation and migration
3) increase vascular permeability
What is the receptor type of TGF-b?
serine/threonine kinase
What are the target cells for TGF-b?
fibroblasts and leukocytes
What are the cells of origin for TGF-b?
macrophages, endothelial, fibroblast, lymphocytes and platelets
What is the main function of TGF-b?
promotes fibrogenesis
What is the function of HGF (hepatocyte growth factor)?
mitogenic for most epithelial cells
What is the receptor for HGF?
c-MET proto-oncogene
What are the functions of IGF-1?
stimulates collagen synthesis by fibroblasts and facilitates fibroblast proliferation
What are the 3 cytokines involved in wound repair?
Interferon, IL-1 and TNF
What are the cells of origin for Interferon?
T cells
What are the target cells of interferon?
macrophages and fibroblasts
What is the function of interferon in wound repair?
downregulates collagen synthesis, inhibits fibroblast proliferation and activates macrophages
What are the cells of origin for IL-1?
macrophages
What are the target cells of IL-1?
t cells (inflammatory cells) and fibroblasts
What are the functions of IL-1 in wound repair?
mediates inflammatory cell functions at the site of injury and is a chemokine for neutrophils and fibroblasts
What is the cell of origin for TNF?
macrophages
What are the target cells for TNF?
macrophages and T cells
What are some of TNF’s functions in wound healing?
activates T cells, attracts neutrophils, and activates macrophages and stimulates IL-1 production (autocrine)
What is juxtacrine signaling?
Contact-dependent signaling
What are progenitor cells?
Cells with limited differentiation capabilities
What are the two properties of stem cells?
self-renewal and pluripotent
What are embryonic stem cells derived from?
The inner cell mass of the blastocyte
What are induced pluripotent stem cells (iPS)?
highly differentiated fibroblasts that grow in a petri dish, but then are transduced with genes that produce proteins that take the cells back to embryonic-like stem cells
Which of the stem cells regenerate cells that are lost by normal wear and tear?
adult stem cells
self-renewing epithelia can reconstitute themselves using what 3 mechanisms?
1) increase the # of actively dividing stem cells
2) increase the # of replications of cells within the amplifying population as in the liver
3) decrease the cell-cycle time for each division
What limits true regeneration of injured tissue?
rapid fibroprolifertive response and scar formation
What are the functions of the ECM?
1) Provide turgor by sequestering water or rigidity by sequestering minerals
2) Reservoir for secreted growth factors
3) Framework for cells to adhere, migrate, and proliferate in
4) Mediates cell-cell interactions
5) Site of remodelling during wound healing
What are the two types of ECM?
interstitial space and basement membrane
What 3 macromolecules compose the ECM?
Fibrous structural proteins
Adhesive glycoproteins
Proteoglycans and hyaluronic acid
What is the most common form of collagen in the body?
collagen I
Where is collagen II found?
hyaline and articular cartilages
Where is type IV collagen found and why is it special?
basement membranes; it doesn’t form fibrils
Which is the first collagen deposited during wound healing?
Collagen III
Why is Vitamin C important for wound healing?
it is essential for the hydroxylation of procollagen
Describe how procollagen becomes fully formed collagen
Procollagen–> triple helix that is secreted from the cell –> cleaved to form fibrils –> crosslinking at lysine and proline residues
What is the function of plasma fibronectin?
Stabilizes early clot (fibrin plug)
What is the first extracellular matrix component deposited during wound healing?
fibronectin
What are the functions of fibronectin?
1) Adds structural integrity to clot
2) Chemotactic for many cells
3) Substrate for cellular adhesion (RGD domain)
4) Substrate for other ECM protein attachment and assembly
Where is laminin found?
The basement membrane
What are the functions of laminin?
Substrate for ECM protein binding (heparin, collagen)
Substrate for cell adhesion
(similar to fibronectin)
What are integrins?
surface bound cell adhesion proteins that facilitate cell-to cell adhesion and facilitate cellular interaction with ECM by binding collagen, fibronectin, and laminin
Which transmembrane receptor also links the cytoskeleton of a cell to it’s cell surface?
integrin
what are cadherins?
surface bound cell adhesion proteins that facilitate cell-to cell adhesion between similar cells and facilitate the formation of cell junctions (desmosomes and zonula adherens)
Which CAM is linked to the cytoskeleton through catenins to regulate cell motility, proliferation, and differentiation?
cadherin
What is the function of proteoglycans?
Forms an ECM scaffold for tissue structure and permeability
What is Hyaluronic acid and what is it’s function?
Huge molecule of long repeating polysaccharides without a protein core (in contrast to proteoglycans) that can bind a large amount of water
What are the steps of angiogenesis?
1) vasodilation (NO and VEGF)
2) Degradation of vessel’s basement membrane
3) migration of endothelial cells toward the angiogenic factor
4) proliferation of endothelial cells
5) maturation of endothelial cells
6) recruitment of periendothelial cells to form mature vessels
What are the four steps of wound healing?
1) hemostasis
2) inflammatory
3) proliferative
4) remodeling
What are the three main things that occur in the hemostasis phase of wound healing?
Platelets & fibrin clot (minutes)
Plasma fibronectin aids in clotting
Platelets release cytokines to activate clotting and complement cascades
What are the two main things that occur in the inflammatory phase of wound healing?
Phagocytes (PMNs, macrophages) clear pathogens
Soluble factors facilitate cell migration/proliferation
What are the active cells of the inflammatory phase?
macrophages
What are the 5 main functions of the proliferative phase?
Angiogenesis Formation of granulation tissue Fibroplasia (collagen deposition) Parenchymal cell migration/proliferation (epithelialization) Wound contraction
What are the 3 main things that occur in the remodeling phase of wound healing?
Remodel collagen to form a mature scar
Replace Type III collagen with Type I
Crosslink collagens
What are the main functional cells of the proliferative phase?
fibroblasts
In the hemostasis phase, platelets release thromboxane which causes what?
Transient vasoconstriction & platelet aggregation – lasts about 10 minutes
In the hemostasis phase, platelets release factors like histamine and serotonin which causes what?
vasodilation and vascular permeability–> edema
What mediates wound contraction?
myofibroblasts
What is delayed primary intention?
The wound is initially left open and when the bed of the wound (granulation tissue) is judged to be sufficiently clean, the wound is closed
What is secondary intention?
When the wound is contaminated and not surgically closed. The wound helps from the bottom up independently
