Gf & Wound Healing

Front 1

What are the 3 overlapping phases in wound healing?

Back 1

o hemostasis & inflammation
o tissue formation & proliferation
o tissue remodeling

Front 2

What does wound healing require?

Back 2

inflammatory response, blood clotting formation, angiogenesis & wound contraction

Front 3

What cells come into play with wound healing?

Back 3

• need an interplay of cell type; platalets, macrophages, fibroblasts, epidermal cells and chemical mediators & growth factors
• GF → mediate cell migration (chemotaxis) and proliferation

Front 4

Describe the role of growth factors.

Back 4

• Stimulate cell growth & differentiation & synthesis of new tissue at wound site
• Promote formation of new blood vessels & angiogenic potential (in vitro)
• Active a low concentration 1-10ng/ml
• Function by binding to cell surface receptors

Front 5

Describe the role of Platelets (1st to arrive) & Macrophages secretes epidermal growth factors (EGF).

Back 5

• Very small peptides → epithelial cell proliferation

• mitogen for keratinocytes & fibroblasta
• inhibits HA stimulated acids (stimulating ulcer healing)

Front 6

Describe the role of Platelet derived growth factor.

Back 6

• Synthesized & release from platelets, macs, smooth muscle and endothelial

• Early in wound healing
• Promotes cell migration & proliferation (notably in CT & smooth muscle)
• chemotactic for Macs & Nuetrophils
• mitogen for fibroblasts & smooth muscle
•angiogeneis & collagen production
• wound contraction

Front 7

Describe the role of Transforming Growth Factor (TGF-A).

Back 7

• Produced in tumor cells, platletes, macs & T-helper

• chemotactic & mitogen for macs, epidermal & endothelial
• angiogenic
• stimulated collagen formation by fibroblasts

Front 8

Describe the role of Transforming Growth Factor (TGF-B).

Back 8

• Produced by T- helper cells & NK cells

• Stimulate collagen formation by fibroblasts & attracts Macs
• Initially stimulate migration/proliferation of fibroblast but later inhibits it

Front 9

Describe the role of Fibroblast Growth Factor.

Back 9

•produced in macs, mast cells and endothelial

•acts in paracrine/endocrine
• regulate pituitary & ovarian function, cholesterol & bile acid
• receptors have tyrosine kinase activity
• Mitogen for fibroblasts & angiogenic

Front 10

Describe the role of Insulin-like Factor I.

Back 10

• Somatomedin C
• Resembles proinsulin
• Mediates the effects of GH on cells
• Produces in variety to tissue but notably the liver → works in paracrine & autocrine manner by interacting cell surface receptors (endogenous tyrosine kinase activity)
• Vary with age → low at birth, peak at puberty and decline after
•stimulate cell proliferation & inhibit cell death

Front 11

Describe the role of Insulin- like Factor II.

Back 11

• Greater than the IGF-I levels in adults
• Decline with age
• Binds to IGF-II receptor glycoprotein or IGF-II mannose-6-phosphate receptors

Front 12

Describe the typical GF receptor.

Back 12

• Peptidergic GF interacts with cell surface receptors that exhibit endogenous tyrosine kinase activity, initiate intracellular events → changes cell morphology & promote cellular movement
• TGF-B = endogenous serine/threonine kinase activity
• Binding = pleiotropic responses
o Autophosphorylation & changes in Na+ & Ca2+

Front 13

Describe the mechanism of GF signal transduction.

Back 13

• Cytoplasmic phospholipidase C hydrolyzes PIP2 → IP3 & DAG (second messengers)
o DAG → Pk C → phosphorylate light chain of cytoskeletal myosin
o Pk C → phosphorylates EGF & PDGF receptors and other substrates involved in cells division & movement
o External signal (GF) translated inside the cell

Front 14

Describe factors that reduce the efficacy of the wound healing process.

Back 14

• Oxygen, nutrients and GF must have access to wound bed
• Chronic alcohol consumption, vascular insufficiency, infection or poor nutrition = limit wound healing

• Medication interfere as well
o Aspirin & penicillamine = copper deficiency
o Antibiotics = impact bacteria producing vit. K
• Compromises wound healing
o Improper moisture content, inadequate delivery of O2 and high lactate and CO2 levels
o pH needs to be 5.5-6
o bacterial infection lower than 100,000 per g

• individuals suffering from diabetes, cholestasis or diarrhea also compromise wound healing

Front 15

Describe the role of Vitamin C.

Back 15

o Effective water soluble antioxidant
o Required for hydroxylation of proline & lysine (cross-link)
o Increase dose (above 60-100mg/day) accelerate collagen formation & reduce workload of immune system

Front 16

Describe the role of Vitamin E.

Back 16

o D alpha-tocopherol possesses greatest biological activity
o Effective lipid soluble antioxidant
o Prevents release of arachidonic acid (inflame.)
o Can be directly applied to wound surface

Front 17

Describe the role of Vitamin A.

Back 17

o Stimulates immune system and fibroblast to produce collagen
o Required for growth and regeneration of epithelial tissue

Front 18

Describe the role of Zinc.

Back 18

o Required for DNA polymerase & superoxidase and superoxide dismutase activity as well as maintaining collagen
o Pregnant & breast feeding woman, and vegetarians = most at risk for deficiency
o Treatment of rheumatoid arthritis

Front 19

Describe the role of Selenium & Copper.

Back 19

o Selenium = cofactor of glutathione peroxidase
o Copper = cofactor of lysyl oxidase

Front 20

Describe the role of Becaplermin.

Back 20

• Human recombinant GF = becaplermin (recombinant platelet-derived GF)
o Treatment of diabetic neuropathic ulcers
o Accelerate wound healing
o Some recurrence