ECM homeostasis

Question 1

What is the extracellular matrix (ECM)?

Answer 1

A network of fibrous proteins and hydrated proteoglycans surrounding cells in tissues, providing strength, support, and communication.

Question 2

Why is the ECM not an inert framework?

Answer 2

It actively guides cell migration and polarity, supports intercellular communication, and is involved in tissue remodelling.

Question 3

How is a healthy ECM maintained?

Answer 3

Through a balance of synthesis and breakdown of matrix molecules.

Question 4

Name three critical roles of the ECM.

Answer 4

1. Provides strength and support to tissues.
2. Guides cell migration and polarity.
3. Permits intercellular communication.

Question 5

What happens if there is an imbalance in ECM turnover?

Answer 5

It leads to diseases such as tissue scarring, fibrosis, cancer, arthritis, or metastasis.

Question 6

What enzymes are responsible for ECM breakdown?

Answer 6

Proteinases (biological scissors).

Question 7

What are the main categories of proteinases?

Answer 7

1. Aspartic proteinases
2. Cysteine proteinases
3. Threonine proteinases
4. Serine proteinases
5. Metalloproteinases

Question 8

What conditions favour the activity of different proteinases?

Answer 8

Low pH: Aspartic and certain cysteine proteinases (e.g., Cathepsin D, B, K).
Neutral pH: Serine and metalloproteinases (e.g., Elastase, MMPs).

Question 9

Name three subfamilies of metalloproteinases and their roles.

Answer 9

1. MMPs (Matrix Metalloproteinases): Breakdown ECM components.
2. ADAMs: Membrane-bound modifiers of ECM.
3. ADAMTS: Secreted ECM proteases like aggregenases.

Question 10

What is the role of MMP-7?

Answer 10

Influences neutrophil migration and releases VEGF and TNF-α for angiogenesis.

Question 11

Which MMPs are involved in collagen degradation?

Answer 11

Collagenases (MMP-1, -8, -13, -18).

Question 12

How are metalloproteinases regulated?

Answer 12

1. By α2 macroglobulin in blood.
2. By Tissue Inhibitors of Metalloproteinases (TIMPs), which block active sites.

Question 13

What activates metalloproteinases?

Answer 13

Removal pf the pro-region by other proteinases, exposing the catalytic Zn2+ binding domain.

Question 14

How does the ECM damage influence repair?

Answer 14

ECM fragments stimulate cell signalling through receptors (integrins and PRR) to regulate further synthesis or inflammation.

Question 15

What role do ECM fragments play in inflammation?

Answer 15

They activate receptors like PRRs, triggering inflammatory cytokine production (e.g., IL-1, TNF-a, TGF-β).

Question 16

What maintains ECM homeostasis during stress?

Answer 16

ECM fragments induce synthesis of new ECM components.

Question 17

How does excessive ECM breakdown lead to cancer?

Answer 17

By promoting tumour survival, migration, and tissue invasion.

Question 18

What happens if ECM feedback induces excessive inflammation?

Answer 18

It leads to irreversible ECM loss and tissue damage.

Question 19

Why is ECM remodelling crucial during development?

Answer 19

It allows for tissue morphogenesis and proper organ formation.

Question 20

What roles do MMPs play in wound healing?

Answer 20

MMP-1 facilitates keratinocyte migration.
MMP-7 releases VEGF and TNF-α for angiogenesis.

Question 21

What are the key domains of MMPs?

Answer 21

1. Catalytic domain (binds Zn2+ for substrate specificity).
2. Haemopexin domain (mediates substrate binding).

Question 22

Which MMPs lack the haemopexin domain?

Answer 22

MMP-7, -23, -26.

Question 23

How many genes encode proteinases in the human genome?

Answer 23

570 genes (~2% of all genes).

Question 24

Which proteinase category is most abundant?

Answer 24

Metalloproteinases (191 genes).

Question 25

How can ECM breakdown be monitored?

Answer 25

By detecting neo-epitopes generated by specific MMPs or ADAMTS enzymes.

Question 26

Which enzymes generate cartilage fragments like hyaluronic acid (HA) neo-epitopes?

Answer 26

ADAMTS-4 and -5.

Question 27

Name three diseases linked to ECM breakdown.

Answer 27

Arthritis, fibrosis, and cancer.

Question 28

How does ECM turnover influence tumour suppression?

Answer 28

Balanced ECM turnover prevents the creation of an environment that supports tumour invasion.

Question 29

What is the role of metalloproteinases in angiogenesis?

Answer 29

They release growth factors (e.g., VEGF) essential for forming new blood vessels.

Question 30

How does inflammation influence ECM catabolism?

Answer 30

Inflammatory cytokines (e.g., TNF-α, IL-1) stimulate metalloproteinase activity, accelerating ECM breakdown.

Question 31

What happens during ECM remodelling in embryonic development?

Answer 31

Controlled breakdown and synthesis of ECM guide cell differentiation and tissue formation.

Question 32

What is the role of TIMPs in cancer prevention?

Answer 32

They inhibit metalloproteinase activity, limiting excessive ECM breakdown that facilitates tumour invasion.