Ecm Homeostasis

Question 1

What Is homeostasis

Answer 1

Balance between ecm synthesis and breakdown (catabolism)

Question 2

Is the ecm an inert framework

Answer 2

No consistently broken down and changing

Question 3

What is ecm homeostasis changes called

Answer 3

Ecm remodelling

Question 4

How do cells around ecm allow for homeostasis

Answer 4

Secrete ecm products like collagen but also secrete enzymes which break them down

Question 5

What must cells get before breakdown catabolism occurs

Answer 5

A stimuli

Question 6

What can too much ecm cause

Answer 6

Fibrosis /scarring or cancer

Eg by excess collagen

Question 7

What can too much catabolism cause

Answer 7

Osteoarthritis, developmental deficiency , metastasis

Question 8

What is one stimuli that causes catabolism

Answer 8

Excess pressure

Question 9

Which type of enzymes cause catabolism

Answer 9

Proteinases (ic and EC)

Question 10

What are the ic proteinase not to do with ecm breakdown

Answer 10

Enzymes ic which are at low ph

Aspartic,cysteine and threonine proteinases.
Ie the proteasome in ag processing

Question 11

Which ph do EC proteinases work at for ecm catabolism

Answer 11

Neutral ph

Question 12

What are the 2 types of EC proteinases

Answer 12

Serine proteinases (cathepsin G)
Or
Metalloproteinases

Question 13

What is the human degradome

Answer 13

The 570 genes for proteinases eg metalloproteinases

Question 14

How many genes are there for metalloproteinases

Answer 14

191

Question 15

How many domains do all metalloproteinases have

Answer 15

3

Pro domain , catalytic domain zn, substrate specificity domain

Question 16

What is the pro domain for

Answer 16

Removed when secreted outside of cell to activate the metalloproteinases

Question 17

What does the catalytic domain need

Answer 17

Zinc or metals for catalytic activity

Question 18

Name the 3 metalloproteinases

Answer 18

MMP (matrix metalloproteinases)

ADAM (a disintegrin like and metalloproteinase)

ADAMTS (ADAM with a thrombospondin motif)

Question 19

What is the substrate specific domain in mmp which recognise specific sequences on ecm components

Answer 19

Hemopexin/ haemopexin

Question 20

Give examples of mmp

Answer 20

Collagenases mmp-1

Gelatinases

Matrilysins

Membrane type MT

Question 21

Are mmp secreted by cell or membrane bound

Answer 21

Secreted unless membrane type MT mmp

Question 22

What is a disintegrin on adam

Answer 22

Small proteins which block integrin interactions in cell adhesion

Question 23

What is thrombospondin which makes adamts unique

Answer 23

Adhesion gp which allows cell to cell or cell to matrix interaction

Question 24

Which metalloproteinases are membrane bound not secreted

Answer 24

Adam

Question 25

Give 2 examples of adamts

Answer 25

Aggrecanases | Pro collagenases

Question 26

What substrate specific domain do adam and adamts have

Answer 26

Dis-sp1

Question 27

What is released due to ecm breakdown

Answer 27

Things bound like gf,hormones and cytokines

Question 28

What are metalloproteinases secreted as and then how is this stopped

Answer 28

Pro enzymes inactive (except Adam) Pro bait region removed

Question 29

Which 2 inhibitors are there for metalloproteinases

Answer 29

A2 macroglobulin (inhibitor in blood) Timps (tissue inhibitors)

Question 30

How do timps work

Answer 30

Slot into active site of metalloproteinases

Question 31

What are neo epitopes

Answer 31

The ecm fragments which are from catabolism eg aggrecanase cuts at specific sites

Question 32

How is ecm breakdown monitored

Answer 32

Antibody searching for neo epitopes

Question 33

What do fragments / neo epitopes allow for homeostasis

Answer 33

Allow stimulation of more ecm to be produced in return of catabolism

Question 34

Why is mmp1 important for wound healing

Answer 34

Allows for keratinocytes migration which produce new epidermal layers

Question 35

Why is mmp7 important for wound healing

Answer 35

Allows neutrophil migration Also release of vegf and TNFa for angiogenesis

Question 36

What can cause abnormal ecm building to promote tumours/cancer

Answer 36

Cross linking of collagen and cancer fibroblast production This then allows other things like tumour angiogenesis

Question 37

After metalloproteinases action, how are they stopped

Answer 37

Endocytosed into cell and then lysosome degradation

Question 38

Which 2 things on cells recognise ecm fragments after catabolism

Answer 38

Integrins Or Prr (the fragments are DAMPS)

Question 39

What does binding to prr by fragments cause

Answer 39

Inflammation via release of cytokines either causing synthesis or Further breakdown

Question 40

Which 3 cytokines released after prr binding cause synthesis and block breakdown

Answer 40

Tgf b-1 Igf-1 Bfgf

Question 41

Which 2 cytokines cause further breakdown which causes diseases

Answer 41

Tnf-a and Il-1

Question 42

Other than tgf b , igf 1 and bfgf what blocks breakdown

Answer 42

Il 6