Ecm Homeostasis Flashcards

1
Q

What Is homeostasis

A

Balance between ecm synthesis and breakdown (catabolism)

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2
Q

Is the ecm an inert framework

A

No consistently broken down and changing

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3
Q

What is ecm homeostasis changes called

A

Ecm remodelling

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4
Q

How do cells around ecm allow for homeostasis

A

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

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5
Q

What must cells get before breakdown catabolism occurs

A

A stimuli

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6
Q

What can too much ecm cause

A

Fibrosis /scarring or cancer

Eg by excess collagen

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7
Q

What can too much catabolism cause

A

Osteoarthritis, developmental deficiency , metastasis

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8
Q

What is one stimuli that causes catabolism

A

Excess pressure

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9
Q

Which type of enzymes cause catabolism

A

Proteinases (ic and EC)

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10
Q

What are the ic proteinase not to do with ecm breakdown

A

Enzymes ic which are at low ph

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

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11
Q

Which ph do EC proteinases work at for ecm catabolism

A

Neutral ph

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12
Q

What are the 2 types of EC proteinases

A

Serine proteinases (cathepsin G)
Or
Metalloproteinases

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13
Q

What is the human degradome

A

The 570 genes for proteinases eg metalloproteinases

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14
Q

How many genes are there for metalloproteinases

A

191

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15
Q

How many domains do all metalloproteinases have

A

3

Pro domain , catalytic domain zn, substrate specificity domain

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16
Q

What is the pro domain for

A

Removed when secreted outside of cell to activate the metalloproteinases

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17
Q

What does the catalytic domain need

A

Zinc or metals for catalytic activity

18
Q

Name the 3 metalloproteinases

A

MMP (matrix metalloproteinases)

ADAM (a disintegrin like and metalloproteinase)

ADAMTS (ADAM with a thrombospondin motif)

19
Q

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

A

Hemopexin/ haemopexin

20
Q

Give examples of mmp

A

Collagenases mmp-1

Gelatinases

Matrilysins

Membrane type MT

21
Q

Are mmp secreted by cell or membrane bound

A

Secreted unless membrane type MT mmp

22
Q

What is a disintegrin on adam

A

Small proteins which block integrin interactions in cell adhesion

23
Q

What is thrombospondin which makes adamts unique

A

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

24
Q

Which metalloproteinases are membrane bound not secreted

A

Adam

25
Q

Give 2 examples of adamts

A

Aggrecanases

Pro collagenases

26
Q

What substrate specific domain do adam and adamts have

A

Dis-sp1

27
Q

What is released due to ecm breakdown

A

Things bound like gf,hormones and cytokines

28
Q

What are metalloproteinases secreted as and then how is this stopped

A

Pro enzymes inactive (except Adam)

Pro bait region removed

29
Q

Which 2 inhibitors are there for metalloproteinases

A

A2 macroglobulin (inhibitor in blood)

Timps (tissue inhibitors)

30
Q

How do timps work

A

Slot into active site of metalloproteinases

31
Q

What are neo epitopes

A

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

32
Q

How is ecm breakdown monitored

A

Antibody searching for neo epitopes

33
Q

What do fragments / neo epitopes allow for homeostasis

A

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

34
Q

Why is mmp1 important for wound healing

A

Allows for keratinocytes migration which produce new epidermal layers

35
Q

Why is mmp7 important for wound healing

A

Allows neutrophil migration

Also release of vegf and TNFa for angiogenesis

36
Q

What can cause abnormal ecm building to promote tumours/cancer

A

Cross linking of collagen and cancer fibroblast production

This then allows other things like tumour angiogenesis

37
Q

After metalloproteinases action, how are they stopped

A

Endocytosed into cell and then lysosome degradation

38
Q

Which 2 things on cells recognise ecm fragments after catabolism

A

Integrins

Or

Prr (the fragments are DAMPS)

39
Q

What does binding to prr by fragments cause

A

Inflammation via release of cytokines either causing synthesis or Further breakdown

40
Q

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

A

Tgf b-1
Igf-1
Bfgf

41
Q

Which 2 cytokines cause further breakdown which causes diseases

A

Tnf-a and Il-1

42
Q

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

A

Il 6