Regeneration, repair, and wound healing

Question 1

regeneration

Answer 1

restoration of damaged or lost cells or tissues to their original state
requires intact ECM scaffold and cell proliferation

Question 2

repair

Answer 2

combination of regeneration and scar formation by deposition of collagen, usually occurs when ECM is damaged and new ECM (collagen) is laid down

Question 3

labile cells

Answer 3

continuously cycling ex skin epithelium

Question 4

quiescent cells

Answer 4

stable cells not actively dividing but able to re-enter cell cycle at G1 and divide ex liver, kidney, pancreas

Question 5

terminally differentiated cells

Answer 5

permanent, do not divide ex neurons, cardiac myocytes

Question 6

regulation of cell cycle

Answer 6

Cyclin D binds to cyclin dependent kinase after signal from growth factor, kinase becomes active and phosphorylates retinoblastoma (main controller of G1 to S transition).
Rb releases E2F so E2F can go to promoter site and translate S phase proteins

Question 7

endocrine

Answer 7

hormones released into bloodstream to reach target cells (steroid hormones)

Question 8

paracrine

Answer 8

cells release soluble factors directed to target cell in the immediate vicinity (neurotransmitters)

Question 9

autocrine

Answer 9

cells respond so substances they release themselves (TGF beta)

Question 10

juxtacrine

Answer 10

target cells bind a signaling molecule bone the plasma membrane of the signaling cells (some EGFs)

Question 11

epidermal growth factor

Answer 11

• receptor is EGFR1, tyrosine kinase
• juxtacrine mechanism
• cells of origin: macrophages, inflammatory cells, platelets
• target cells: epithelial cells, fibroblasts
• effects: cellular proliferation

Question 12

platelet derived growth factor

Answer 12

• receptor is PDGFRa/B, tyrosine kinase
• cells of origin: platelet granules, macrophages, endothelial cells, fibroblasts
• target cells: mesenchymal cells (NOT epithelial cells), hematopoietic cells and fibroblasts
• effects: chemokine and mitogen for mesenchymal cells, stimulates fibroblasts to secrete ECM and collagenase

Question 13

fibroblast growth factor

Answer 13

• receptor is tyrosine kinase, requires FGF to be bound to ECM syndecan in order to activate receptor
• cells of origin: epithelial cells, macrophages
• target cells: fibroblasts, endothelial cells
• effects: fibroblast chemotaxis, proliferation, ECM deposition, angiogenesis

Question 14

vascular endothelial growth factor

Answer 14

• receptor tyrosine kinase
• cells of origin: mesenchymal cells, leukocytes, fibroblasts
• target cells: endothelial cells
• effects: angiogenesis, endothelial cell proliferation and migration, vascular permeability

Question 15

transforming growth factor beta

Answer 15

• polypeptide growth factor, receptor is serine/ threonine kinase
• cells of origin: platelets, endothelial cells, fibroblasts, macrophages
• target cells: fibroblasts, leukocytes
• functions: many, some contradictory. promote fibrogenesis

Question 16

interferon

Answer 16

cytokine produced by T cells that targets macrophages and fibroblasts to activate macrophages, down-regulate collagen synthesis, inhibit fibroblast proliferation

Question 17

IL-1

Answer 17

cytokine produced by macrophages that targets inflammatory cells and fibroblasts to mediate immune functions in the wound and is chemotactic for neutrophils and fibroblasts

Question 18

TNF

Answer 18

cytokine produced by macrophages and T cells that targets macrophages and T cells. autocrine function in macrophages- causes IL-1 production. activates T cells, induced collagen production in fibroblasts, attracts neutrophils

Question 19

stem cell properties

Answer 19

have not terminally differentiated, can regenerate lost cells, self renewal, asymmetric replication

Question 20

embryonic stem cells

Answer 20

derived from inner mass of blastocyst, pluripotent

Question 21

induced pluripotent

Answer 21

adult fibroblasts treated with gene products revert to pluripotent stem cells

Question 22

adult stem cells

Answer 22

adult stem cell reservoirs in certain tissues, limited in differentiation potential

Question 23

collagen

Answer 23

triple helix polypeptide chains modified by glycosylation and hydroxylation
Type IV is non-fibrilar and found in basement membrane

Question 24

elastic fibers

Answer 24

composed of a core of elastin surrounded by fibrillin

Question 25

fibronectin

Answer 25

plasma form stabilizes early clot, cellular form is secreted from fibroblasts, macrophages, endothelial cells binds numerous molecules first ECM deposited during wound healing

Question 26

laminin

Answer 26

found in basement membrane in network with Type IV collagen, similar functionally to fibronectin

Question 27

intigrins

Answer 27

transmembrane receptors that facilitate cell-cell adhesion facilitates cellular interaction with ECM by binding fibronectin, laminin, collagen links cell surface to the cytoskeleton (signal transduction)

Question 28

cadherins

Answer 28

faciliatates cell-cell adhesion between similar cell types facilitates formation of cell junctions liked to cytoskeleton through catenins to regulate cell motility, proliferation, differentiation

Question 29

proteoglycans

Answer 29

Repeating polymers of disaccharides (chondroitin sulfate, heparan sulfate, dermatan sulfate) bound to a protein core Forms an ECM scaffold for tissue structure and permeability

Question 30

hyaluronic acid

Answer 30

repeating polysaccharide molecule that binds water to form viscous hydrated gel

Question 31

hemostasis phase of wound healing

Answer 31

platelets aggregate and secrete inflammatory agents serum fibrin/fibronectin form a plug at site of injury platelets release thromboxane-> initial vasoconstriction followed by histamine-induced vasodilation, edema

Question 32

inflammatory phase of wound healing

Answer 32

early: neutorphils, Attracted by chemokines (fibronectin, PDGF, TGF-b, C5b, TNF) intermediate: macrophages, secrete growth factors, cytokines, proteases late: neutrophils and macrophages decline, fibroblasts are prominent

Question 33

proliferative phase of wound healing

Answer 33

``` angiogenesis formation of granulation tissue fibroplasia (TGF-B) epithelialization wound contraction (myofibroblast differentiation induced by TGF-B) ```

Question 34

maturation phase of wound healing

Answer 34

degradation of collagen and ECM by matrix metalloproteinases-remodeling replacement of HA with proteoglycans

Question 35

local factors affecting wound healing

Answer 35

type, size, location of wound; vascular supply, oxygen supply; infection; necrosis; foreign material; movement; radiation

Question 36

systemic factors affecting wound healing

Answer 36

circulatory compromise; nutritional status (protein, zinc, vitamin C, vitamin A-re-epithelialization, thiamine/ riboflavin); diabetes; obesity; hormones; chemotherapy