Extracellular matrix

Question 1

What are the functions of the extracellular matrix?

Answer 1

Cellular division
Motility
Differentiation
Adhesion
Structure

Question 2

What secretes the extracellular matrix?

Answer 2

Cell secretes macromolecules for ECM

Question 3

What are the main components of ECM?

Answer 3

Structural proteins (Collagen, Elastin)

Proteoglycans (protein-polysaccharides)

Adhesive Glycoproteins (Fibronectins, Laminins)

Question 4

What is the purpose for collagens & elastins in the ECM

Answer 4

Provide strength & flexibility

Question 5

What is the purpose for proteoglycans in the ECM?

Answer 5

Provide matrix for collagens and elastins to embed within

Question 6

What is the purpose of Adhesive glycoproteins in ECM?

Answer 6

Attach cells to matrix

Question 7

How much of total body protein is collagen?

Answer 7

25-30%

Question 8

Polypeptides of collagen

Answer 8

Triple helix of glycine, hydroxylysine, hydroxyproline

Question 9

How much weight can collagen hold?

Answer 9

1mm fiber = 20 lbs

Question 10

How many different collagen genes are there?

Answer 10

25 different alpha chains

Question 11

What provides collagen with it’s strength?

Answer 11

Cross-linked collagen bundles

Question 12

What causes loss of joint function during aging?

Answer 12

Abnormal collagen cross-linking

Question 13

What is the symptom of collagen synthesis deficiency?

Answer 13

Hypermobility of joints

Question 14

What is elastin made of?

Answer 14

Proteins with Glycine & Proline with no hydroxylation

Elastin is crosslinked between lysines

Question 15

What causes wrinkles and inflexible joints?

Answer 15

Loss of elastin with aging

Question 16

What is Supravalvular aortic stenosis? (SVAS)

Answer 16

Mutations in elastin gene disrupt elastin synthesis and result in narrowing of aorta or pulmonary vessels

Question 17

WHat are proteoglycans?

Answer 17

Glycoproteins with glycosaminoglycans

Question 18

What are the glycosaminoglycan side chains?

Answer 18

Chondroitin sulfate
Keratan Sulfate
Heparin

Question 19

What is the purpose for glycosaminoglycans?

Answer 19

Receptors, filtration, shock absorption, water retenetion

Question 20

What is hyaluronate?

Answer 20

Proteoglycan that acts as backbone in collagen

Question 21

What is the function of hyaluronate?

Answer 21

Lubricates any place with friction

Question 22

What is Heparin/Heparan SUlfate?

Answer 22

Heparan Sulfate is found in every cell body, role in inflammation

Heparin is an anticoaglant

Question 23

WHat is fibronectin?

Answer 23

Most common adhesive glycoprotein

Can be soluble, insoluble or partially soluble depending on splicing

Question 24

What is the main function for fibronectin?

Answer 24

Maintains cell shape

Blood clotting (soluble form)

Guides immune cells to wound

Question 25

What role does fibronectin play in cancer?

Answer 25

Carinomas are unable to synthesize fibronectin and cells lose their shape and detach from ECM Giving fibronectin revert cells to normal shape and cells are no longer malignant

Question 26

Where are laminins located?

Answer 26

Basal laminae under epithelial cells in muscle, fat and schwann cells Separates ECM from epithelial cells

Question 27

What is the function of the basal lamina?

Answer 27

Structural support | Selective permeability barrier

Question 28

Why is the basal lamina important in cancer?

Answer 28

May allow the migration of cancer cells

Question 29

What does disorded extracellular matrix remodeling lead to?

Answer 29

Scar formation

Question 30

What tissues does the ECM provide a structural matrix for

Answer 30

All tissues Bone & Cartilage specifically

Question 31

Why is remodeling constant in the ECM?

Answer 31

Allows cells to be responsive to needs of the animal

Question 32

What sites and cells is the ECm most active?

Answer 32

Cartilage (Chondrocytes) Bone (Osteocytes) Tendon (fibrocytes) Crnea (Fibrocytes)

Question 33

What are the parent cells of ECM and how do they regulate ECM?

Answer 33

Osteoblasts Chondrocyte Fibrocytes Transcriptional regulation

Question 34

What do ECM cells respond to?

Answer 34

Paracrine signaling (Growth factors) Physical signaling from other cells/ECM

Question 35

How is ECM degraded?

Answer 35

Metallproteinase enzymes | Serine proteases

Question 36

What are the characteristics of metalloproteinase?

Answer 36

Requires zinc or calcium | Specific for 1 ECM compoenent

Question 37

Are degradation enzymes auto-upregulated?

Answer 37

Yes, in pathways with a high turnover of ECM

Question 38

What are the Tissue Inhibitors of metalloproteinase?

Answer 38

TIMP 1,2,3,4 Irreversibly bind to metalloproteinase

Question 39

What are the Serine Protease inhibitors?

Answer 39

Alpha 1-antrypsin

Question 40

What is Alpha 1-antrypsin deficiency?

Answer 40

A lack of Alpha 1-antrypsin serine protease inhibitor leads to excessive degradation of elastin by the neutrophil elastase enzyme

Question 41

What diseases are caused by alpha 1-antrypsin deficiency?

Answer 41

Emphysema, COPD, cirrhosis

Question 42

Treatment of alpha 1-antrypsin deficiency?

Answer 42

Intravenous infusions of alpha 1-antrypsin

Question 43

What is panniculitis?

Answer 43

Alpha 1-antrypsin deficiency in dogs can cause hardening of the skin in to painful, hard lumps and patches Can occur in a range of severity and age