Matrix metalloproteinases

Author: Prof. Dr. med. Peter Altmeyer

Last updated on: 29.10.2020

Synonym(s)

MMP

Definition
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Group of more than 20 zinc-dependent endopeptidases with high proteolytic activity and partially overlapping substrate specificity for protein building blocks of the extracellular matrix

Classification
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Subfamilies:

Collagenases
Gelatinases
Stromelysine
Membrane-associated matrix metalloproteinases (membrane-type; MT1-MMP, MT2-MMP)
More MMP's.

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General information
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MMPs have physiological functions in processes where the formation of new basement membranes takes place (e.g. fetal growth of skin and skin appendages, wound healing, angiogenesis) and are involved in pathological processes with undesired degradation of extracellular matrix and basement membranes. The expression of MMP's is regulated by a complex interplay of inductors (e.g. IL-1, PFGF, UVB-rays, TNF-α, growth factors) or suppressors or inhibitors (e.g. retinoids, heparin, glucocorticoids, natural tissue inhibitors (TIMP's), tetracyclines, antracyclines). Matrix metalloproteinases are expressed on the surface of inflammatory cells and support eosinophilic granulocytes, neutrophil granulocytes, lymphocytes, histiocytes and other cells in migrations in inflammatory processes. Reduced expression of MMPs leads to increased storage of extracellular matrix proteins in the skin during fibrosis processes. The degradation of basement membranes and the formation of tumor blood vessels is supported by MMPs in carcinogenesis processes.

Matrix metalloproteinases are involved in pathological processes in:

lichen planus
Scleroderma
Keloids
Epidermolysis bullosa dystrophica inversa
Wound healing
Lipodermatosclerosis
venous leg ulcer
Skin aging (influence of UV light)
Basal cell carcinoma
Malignant melanoma.

Literature
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Baker AH (2002) Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 115: 3719-3727
Brenneisen P et al (2002) Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events. Ann N Y Acad Sci 973: 31-43
Chen GS et al (2006) Differential expression of matrix metalloproteinase-2 by fibroblasts in co-cultures with keratinocytes, basal cell carcinoma and melanoma. J Dermatol Sep 33: 609-615
Heroy Y et al (1999) Gene and protein family of matrix metalloproteinases. dermatologist 50: 825-836
Hofmann UB et al (2002) Importance of matrix-degrading enzymes for melanoma progression. dermatologist 53: 587-595
Pilcher BK et al (1999) Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity. Ann NY Acad Sci 878: 12-24

Tables
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enzyme	MMP number	Substrates
Collagenases
Interstitial collagenase/ fibroblast collagenase	MMP-1	collagen type I, II, III, VII, VIII, X, entactin, aggrecan, versican
PMN collagenase Neutrophil collagenase	MMP-8	Collagen type I, II, III, V, VII, VIII, X, aggrecan, fibronectin
collagenase-3	MMP-13	Collagen type I, II, III, IV, gelatin, aggrecan, perlecan, tenascin C
Collagenase-4 (Xenopus)	MMP-18	Collagen type I
Gelatinases
gelatinase A	MMP-2	Collagen type I, IV, V, VII, X, XI, aggrecan, versican, fibronectin, laminin, elastin, tenascin C,
Gelatinase B	MMP-9	collagen type IV, V, VII, X, XIV, aggrecan, elastin, fibronectin
Stromelysine
Stromelysin-1/ Transin-1	MMP-3	collagen type III, IV, IX, X, gelatin, aggrecan, versican, fibronectin, laminin, fibrinogen
Stromelysin-2/ Transin-2	MMP-10	collagen type III, IV, V, elastin, aggrecan, fibronectin
stromelysin-3	MMP-11	alpha-proteinase inhibitor
Membrane-associated MMPs
MT1-MMP	MMP-14	Collagen type I, II, III, fibronectin, laminin, vitronectin, aggrecan
MT2-MMP	MMP-15	Laminin, fibronectin, gelatin, tenascin C
MT3-MMP	MMP-16	Activator of proMMP-2
MT4-MMP	MMP-17	not known
MT5-MMP	MMP-24	proMMP-2, proMMP-9, gelatin
MT6-MMP	MMP-25	collagen type IV, fibronectin, fibrin
Further MMPs
Matrilysin Matrine PUMP-1	MMP-7	Collagen type IV, X, aggrecan, fibronectin, laminin, elastin, entactin, tenascin C, fibronectin, transferrin
Metalloelastase/ Macrophage Elastase	MMP-12	collagen type IV, gelatin, fibronectin, laminin, elastin, fibronectin
not known	MMP-19	collagen type IV, gelatin, fibronectin, laminin, elastin, tenascin C, fibronectin, a-proteinase inhibitor
Enamelysin	MMP-20	Amelogenin