Matrix formation

Question 1

ECM breakdown

Answer 1

The main players in ECM breakdown are MMPs, these can be inhibited by TIMPs. Other proteins which can degrade ECM are serine proteases and cathepsins and heparanases.

Question 2

ECM formation

Answer 2

by cells. Under the influence of cytokines, growth factors, signaling pathways, etc. The ECM consists of multiple ECM proteins.

Question 3

Ways to limit fibrosis

Answer 3

• The TGF-b pathway is a big target. Small molecules are often not effective enough. Antagonists of the pathway are used or other molecules to inhibit transcription of ECM targets
• MMPs and other remodeling enzymes as target - Interfere with chemokines
• Induce re-uptake of ECM proteins - Injection of decellularized ECM
• Integrins as target

Question 4

Initiation and progression of fibrosis

Answer 4

There is an important distinction between the initiation of fibrosis and the progression of fibrosis. Initiation of fibrosis is needed for wound healing, but if it progresses into impairment of the organ function, the fibrosis is pathological. The process of fibrosis is reversible if
- The wounding is integumentary (involving skin, so no deep wounds?)
- The injury is acute and the cause is controlled
Progression of fibrosis has both cell- and ECM-driven mechanisms. Fibrogenic mesenchymal progenitor cells have fibrogenicity from itself. Some ECM components are fibrogenic and the ECM induces certain processes involved in fibrosis (like myofibroblasts differentiation).