Table 1.

Proteolytic Enzymes, their regulators, and downstream effects.

Proteolytic System	Enzymes	Activators	Inhibitors	Activity	Citation
Fibrinolytic	Plasminogen- inactive	▪Tissue-type plasminogen activator (t-PA) (Predominantly in blood circulation) ▪Urokinase-type plasminogen activator (u-PA) (Activates cell bound plasminogen)	▪α2 antiplasmin ▪Plasminogen activator inhibitors (PAI-1/2)	▪Degrades Fibrin into soluble degradation products ▪Activates some MMPs	[147,152,156]
	Plasmin-Active
Collagenases	MMP1 (Collagenase 1)	▪VEGF induces MMP1 expression	▪TIMPs	▪Digest Fibrillar Collagen ▪ASC-derived MMP1 promotes vascular sprouting	[160,161,162]
	MMP13 (Collagenase 3)	▪MT1-MMP activates proMMP13		▪Digest Fibrillar Collagen ▪Enhances over the course of adipose differentiation
	MT1-MMP	▪Regulated by proprotein convertase	▪Inhibited by TIMP2	▪Degrade Type 1 Collagen to promote three-dimensional adipocyte lipid accumulation through matrix rigidity regulation ▪Promotes tubulogenic activity of endothelial cells	[158,159,163]
Gelatinases	MMP2 (Gelatinase A)	▪Direct activation of proMMP2 (progelatinase A) is achieved in a plasmin independent mechanism ▪Activated through TIMP2 and homo-dimerization of MT1-MMP ▪During angiogenesis-serine proteinase plasmin activates	▪Ro 28-2653 ▪Tolylsam ▪TIMP-1 (B) ▪TIMP-2 (A)-without MT1-MMP	▪Fragments Basement Membrane, Collagen, and Gelatin promoting endothelial proliferation, chemotaxis, and angiogenesis ▪Mediates adipocyte migration and clustering to form lobular architecture	[42,43,158,164,165,166,167]
	MMP9 (Gelatinase B)	▪Activation of proMMP9 (progelatinase B) is achieved by plasmin	▪TIMP’s	▪Release of fibrinogen and fibronectin which lay the provisional foundation for the migration of additional endothelial cells ▪Promotes adipocyte differentiation	[40,41,42,43,44,89]