L10

Question 1

what is the ECM

Answer 1

is a network of fibrous proteins and hydrated proteoglycans which surround cells in tissues

Question 2

what are the functions of the ECM

Answer 2

provides strength and support

guides cell migration and polarity

permits intercellular communication

Question 3

what does Maintenance of a healthy ECM depend on

Answer 3

balance between synthesis and breakdown of matrix molecules

Question 4

How is a healthy ECM maintained

Answer 4

cells within ECM secrete the components of the ECM

the same cells also secrete enzymes which digest/breakdown these components

to remove damaged matrix
i.e. ‘remodel” matrix

Question 5

what happens when matrix synthesis is higher than its breakdown

Answer 5

tissue scarring, fibrosis, cancer
(alteration of function)

Question 6

what happens when matrix breakdown is higher than its synthesis

Answer 6

developmental/induced deficiencies/breakdown, Arthritis/metastasis
(loss of function)

Question 7

what are proteinases

Answer 7

enzymes that break down proteins

Question 8

what proteinases are intracellular

Answer 8

aspartic proteinases

cysteine proteinases

threonine proteinases

Question 9

what proteinases are extracellular

Answer 9

serine proteinases

metallo-proteinases

Question 10

what is the degradome

Answer 10

570 genes in in the human genome that encode proteinases

Question 11

what are the domains of metalloproteinase

Answer 11

pre

pro

catalytic domain (CD)

substrate specific domain

Question 12

which domain binds Zn 2+

Answer 12

CD

Question 13

what domains are removed during secretion

Answer 13

Pre and Pre

Question 14

what are the types of metalloproteinase

Answer 14

1. MMP (matrix metalloproteinases)
2. ADAM (a disintegrin-like and metalloproteinase)
3. ADAMTS (a ADAM with thrombospondin motifs)

Question 15

what additional domain do ADAMs have that MMPs don’t

Answer 15

disintegrin-like domain

Question 16

give examples of MMPs

Answer 16

collagenases (MMP-1, -8, 13, 18)

gelatinases (MMP-2, -9)

stromelysins (MMP-3 -10, -11

matrilsins (MMP-7, -26)

membrane-type ((MT); MMP-14,-15, -16, -17 -23, -24, -25)

Question 17

give a feature of ADAM

Answer 17

mostly membrane bound

Question 18

give a feature for ADAMTS

Answer 18

secreted into ECM like MMPs

Question 19

give examples for ADAMTS

Answer 19

pro-collagenases (ADAMTS-2, -3, -14

aggregenases (ADAMTS-1, -4, -5, -8, -9, -15)

Question 20

The metalloproteinase family are involved in ECM breakdown. what is ECM breakdown called

Answer 20

catabolism

Question 21

Metalloproteinase family work inside the cell

Answer 21

NO

Question 22

what is the substrate specific domain in MMPs

Answer 22

Haemopexin

Question 23

what is the substrate specific domain in ADAM and ADAMTS

Answer 23

DisT SP-1

Question 24

what do metalloproteinase family members (MMP, ADAM, ADAMTS) mediate

Answer 24

breakdown (catabolism) of ECM components and release/activation of growth factors, hormones, cytokines anchored in ECM)

Question 25

what are metalloproteinase family members characterized by

Answer 25

Zn2+ binding catalytic domain secretion into ECM as inactive pro-enzymes activated by removal of pro “bait” region by other proteinases

Question 26

metalloproteinases are highly specific

Answer 26

TRUE

Question 27

what are metalloproteinases inhibited by

Answer 27

alpha 2 macroglobulin tissue inhibitors of metalloproteinases (TIMPs)

Question 28

what are the features of alpha 2 macroglobulin

Answer 28

found in blood ubiquitous proteinase inhibitor

Question 29

what are TIMPs

Answer 29

small secreted proteins which “slot” into active sites of metalloproteinase catalytic domains

Question 30

what are neo-epitopes

Answer 30

epitopes that appear after agricans are cleaved by ADAMTS-4/5 or MMPs

Question 31

what antibody binds to neo-epitopes produced by aggrecanase

Answer 31

BC-3

Question 32

what antibody binds to neo-epitopes produced by MMP

Answer 32

AF-28

Question 33

Loading stress also produces fragments of ECM components. what do these fragments stimulate

Answer 33

increased ECM synthesis

Question 34

when is ECM re-modelling essential

Answer 34

embryonic development wound healing prevention of tumour development

Question 35

which MMP is required for keratinocyte migration in wound healing

Answer 35

MMP-1

Question 36

which MMP influences neutrophil migration in wound healing

Answer 36

MMP-7

Question 37

which MMP releases VEGF and TNF-a allows angiogenesis in wound healing

Answer 37

MMP-7

Question 38

how does ECM re-modelling prevent tumor development

Answer 38

tumor cells make MMPs MMPs degrade the basal lamina around tumor cells tumor cells metastasise and get into the blood for example

Question 39

what are the levels of Controlling metalloproteinase activity

Answer 39

gene expression of ECM proteins localization maturation inhibition degradation

Question 40

how does the Recognition of ECM breakdown products lead to homeostatic control

Answer 40

ECM/fragments are recognized by integrins expressed by many ECM cells. Signaling results in increased ECM synthesis ECM/fragments are also recognized by PRR expressed by many ECM cells. Signaling results in inflammation i.e. production of IL-1, TNF-alpha, TGF-beta

Question 41

what inflammatory cytokines are produced during ECM synthesis

Answer 41

TGF-beta IGF-1 bFGF

Question 42

what inflammatory cytokines are produced during ECM breakdown

Answer 42

IL-1 TNF-alpha