Wound Healing

Question 1

ECM - functions

Answer 1

Mechanical support, scaffolding for tissue renewal, control of cell growth, maintenance of cell differentiation, establishment of tissue microenvironment, storage and presentation of regulatory molecules

Question 2

ECM - forms (2)

Answer 2

-Interstitial matrix - “space filler”
-Basement membrane

Question 3

ECM - components (3)

Answer 3

-Fibrous structural proteins (i.e., collagen and elastin)
-Water hydrated gels (i.e., proteoglycans and HA)
-Adhesive glycoproteins and receptors

Question 4

Collagen - forms and associated types

Answer 4

-Fibrillar (uninterrupted): 1, 2, 3, 5, 11
-Non-fibrillar (interrupted/mesh): 4

Question 5

Type 4 collagen

Answer 5

-Non-fibrillar
-Main component of basement membrane w/ laminin

Question 6

Vitamin C is required for which step in collagen synthesis?

Answer 6

Required for fibrillar collagen assembly, specifically the hydroxylation step

Question 7

Adhesive glycoproteins and receptors - examples

Answer 7

-Fibronectin
-Laminin
-Integrins

Question 8

Stable tissues - definition and examples

Answer 8

Will divide in response to injury or loss of tissue mass
Liver and kidney parenchyma, endothelial cells, smooth muscle

Question 9

Labile tissues - definition and examples

Answer 9

Readily regenerate after injury as long as stem cell pool is preserved
Hematopoietic cells, surface epithelia, transitional epithelia

Question 10

Permanent tissues - definition and examples

Answer 10

Injuries result in scar formation
Neurons and cardiac muscle

Question 11

Driving force for repair

Answer 11

HIF-a

Question 12

Steps in connective tissue repair (scar formation)

Answer 12

Tissue injury –> inflamm –> angiogenesis –> migration and proliferation of fibroblasts –> collagen synthesis –> connective tissue remodeling to fibrous tissue

Question 13

Vasculogenesis

Answer 13

Blood vessel formation during embryonic development - from angioblasts or hemangioblasts

Question 14

Angiogenesis - what is needed?

Answer 14

-Pre-existing vessels
-Endothelial progenitor cells

Question 15

Angiogenesis - growth factors

Answer 15

HIF-a, VEGF and VEGFR2 on endothelial cells

Question 16

Angiogenesis - regulation/control

Answer 16

Notch pathway (helps w/ spacing)

Question 17

Angiogenesis - inhibitors

Answer 17

Angiostatin, endostatin, thrombospondin

Question 18

Angiogenesis - pro-vessel stabilization

Answer 18

Angiopoietin 1, PDGF, TGF-B

Question 19

Angiogenesis - anti-vessel stabilization/pro-remodeling

Answer 19

Angiopoietin 2, MMPs

Question 20

TGF-B - functions

Answer 20

-Fibroblast migration and proliferation
-Inc synthesis of collagen (myofibroblasts)
-Dec degradation of ECM by inhibiting MMPs

Question 21

TGF-B - pathway

Answer 21

SMAD pathway

Question 22

ECM - degradation

Answer 22

MMPs

Question 23

MMPs - activation

Answer 23

Macs, fibroblasts, leukocytes, others

Question 24

TIMPs - definition

Answer 24

Tissue inhibitors of metalloproteases

Question 25

Causes of altered wound healing

Answer 25

Infxn, nutritional issues, glucocorticoids, poor apposition, poor perfusion, foreign bodies

Question 26

Glucocorticoid delay of wound healing

Answer 26

Can inhibit TGF-B and diminish fibrosis

Question 27

Secondary intention healing - differences

Answer 27

-Larger fibrin clot -More exudate and necrotic debris -More intense inflamm -More granulation tissue -Type 3 collagen replaced by type 1 -Wound contraction

Question 28

Wound healing - stages

Answer 28

Hemostasis --> inflammation --> proliferation --> maturation

Question 29

Examples of glycosaminoglycans (GAGs)

Answer 29

Keratan sulfate and chondroitin sulfate

Question 30

Examples of glycoproteins

Answer 30

Fibronectin, integrins, laminins

Question 31

Actions of HIF-a

Answer 31

•Hydroxylated (normal O2 conditions) HIF-a is inactive •Non-hydroxylated HIF-a is active and binds to HRE which upregulates repair mechanisms (VEGF, angiogenesis, glucose metabolism, etc)

Question 32

What is the most important growth factor and its receptor (including location) for early stages of angiogenesis?

Answer 32

VEGF A VAGFR2 on ECs

Question 33

Regulators of angiogenesis

Answer 33

Notch pathway, VEGFR1, and angiogenesis inhibitors (angiostatin, endostatin, thrombospondin)

Question 34

Pro vessel stabilization factors

Answer 34

Angiopoietin 1, PDGF, TGF-B

Question 35

Anti vessel stabilization/pro remodeling factors

Answer 35

Angiopoietin 2, MMPs

Question 36

Functions of TGF-B in wound healing

Answer 36

•Fibroblast migration and proliferation •Inc synthesis of collagen (myofibroblasts) •Dec ECM degradation by inhibit MMPs

Question 37

How TGF-B stimulates fibroblast migration and proliferation

Answer 37

Binds to receptor —> phosphorylates R-SMAD and Co-SMAS to overcome SMAD7 inhibition

Question 38

Signals for activation of MMPs

Answer 38

PDGF, EGF, IL1/TNF

Question 39

MMP inhibitors

Answer 39

TIMPs (made by mesenchymal cells) TGF-B Steroids

Question 40

Factor that promotes fibrosis

Answer 40

TGF-B

Question 41

Stimulator of fibrosis

Answer 41

TGF-B

Question 42

Inhibitory SMAD

Answer 42

SMAD7

Question 43

In angiogenesis, which cell signaling pathway is responsible for inhibiting stalk cell mitosis?

Answer 43

Notch