Metalloproteinases in Inflammatory Bowel Diseases

Figures & data

Table 1 Expression and Function of Various Matrix Metalloproteinases in Inflammatory Bowel Disease

MMP	Alternative Names	Class	Substrates	Expression in IBD Compared to Controls	Number of Controls	Number of Patients	Disease	Type of Tissue	Quantification Technique	References
MMP-1	Collagenase 1	Collagenases	Collagen, gelatin	Increased	8	8, 5, 6, 7	U, UC, E, CD	Tissue	In situ hybridization	[13]
					Not stated	30	UC	Tissue (colon)	qPCR	[20]
					Not stated	17, 16	UC, CD	Tissue	Immunohistochemistry	[32]
					Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray	[38]
					20	30	UC	Tissue (colon)	RT-PCR	[64]
MMP-2	Gelatinase A	Gelatinases	Collagen, gelatin	Unchanged	62	20, 122	UC, CD	Colonic mucosa	ELISA	[34]
					14	23, 22	UC, CD	Tissue	RT-PCR	[35]
MMP-3	Strom elys in 1	Stromelysins	Collagen, gelatin	Increased	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
					9	1 1	CD	Tissue	In situ hybridization	[24]
					10	13, 25	UC, CD	Tissue	ELISA	[33]
					16	23, 24	UC, CD	Tissue	RT-PCR	[36]
					Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray	[38]
MMP-7	Matrilysin 1/ PUMP 1	Stromelysins	Collagen, gelatin, flbronectin, laminin	Increased	Not stated	Not stated	UC, CD	Tissue (colon, cecum)	Microarray, RT-PCR	[19]
					Not stated	52	UC	Tissue (colon, rectum)	Immunohistochemistry	[26]
					Not stated	35	UC	Tissue, mucosa	RT-PCR	[27]
					4	25	UC	Tissue (colon)	Immunohistochemistry	[65]
					19	17, 23, 19	UC, CD, AP	Tissue (polyps)	qPCR	[66]
MMP-8	Collagenase 2	Collagenases	Collagen, gelatin, aggrecan	Increased	11	12, 11	UC, CD	Tissue	Immunohistochemistry	[17]
MMP-9	Gelatinase B	Gelatinases	Collagen, gelatin	Increased	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
					9	1 1	CD	Tissue	In situ hybridization	[24]
					9	31, 13	UC, CD	Tissue	Zymography	[25]
					8	16	UC	Tissue (colon)	qPCR	[29]
					Not stated	17, 16	UC, CD	Tissue	Immunohistochemistry	[32]
					Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray	[38]
					Not applicable	Not applicable	Not applicable	Cells	Zymography	[67]
MMP-10	Stromelysin 2	Stromelysins	Collagen, fibronectin, laminin, elastin	Increased	21	21, 22	UC, CD	Colonic mucosa	qPCR	[15]
					1 1	12, 1 1	UC, CD	Tissue	Immunohistochemistry	[17]
					Not stated	Not stated	UC, CD	Tissue (colon, cecum)	Microarray, RT-PCR	[19]
					Not stated	5	1C	Tissue (explants)	qPCR	[68]
MMP-11	Stromelysin 3	Stromelysins	Collagen, fibronectin, laminin, aggrecan	Unchanged	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
MMP-12	Macrophage metal loelastase	Elastases	Collagen, fibronectin, elastin	Increased	7	10, 7, 14	UC, 1C, CD	Tissue	In situ hybridization	[14]
					11	12, 11	UC, CD	Tissue	Immunohistochemistry	[17]
					Not applicable	Not applicable	UC, CD	Tissue (explants)	Microarray	[22]
MMP-13	Collagenase 3	Collagenases	Collagen, gelatin	Inconclusive	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
					30	35, 24	UC, CD	Tissue (colon)	Immunohistochemistry	[69]
MMP-14	Membrane type 1 MMP	Membrane types	Gelatin, fibronectin, laminin	Inconclusive	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
					14	23, 22	UC, CD	Tissue	RT-PCR	[35]
MMP-I 5	Membrane type 2 MMP	Membrane types	Gelatin, fibronectin, laminin	Insufficient data
MMP-16	Membrane type 3 MMP	Membrane types	Gelatin, fibronectin, laminin	Insufficient data
MMP-17	Membrane type 4 MMP	Membrane types	Fibrinogen, fibrin	Unchanged	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
MMP-19	RASI-I /stromelysin 4	Other	Unknown	Unchanged	Not applicable	Not applicable	Not applicable	Tissue (explants)	Microarray, in situ hybridization	[21]
					5	24, 9, 7, 20	UC, 1C, CD, CRC	Tissue (colon)	Immunohistochemistry	[70]
MMP-20	Enamelysin	Other	Unknown	Insufficient data
MMP-21	X-MMP	Other	Unknown	Insufficient data
MMP-23	CA-MMP	Other	Unknown	Increased	20	40, 30	UC, CD	Tissue (rectum)	RT-PCR	[71]
MMP-24	Membrane type 5 MMP	Membrane types	Unknown	Insufficient data
MMP-25	Membrane type 6 MMP	Membrane types	Unknown	Insufficient data
MMP-26	Matrilysin 2/ Endometase	Other	Unknown	Unchanged	5	24, 9, 7, 20	UC, 1C, CD, CRC	Tissue (colon)	Immunohistochemistry	[70]
MMP-27	MMP-22, C-MMP	Other	Unknown	Insufficient data
MMP-28	Epilysin	Other	Unknown	Decreased	Not stated	35	UC	Tissue, mucosa	RT-PCR	[27]
					5	24, 9, 7, 20	UC, 1C, CD, CRC	Tissue (colon)	Immunohistochemistry	[70]

Abbreviations: AP adenomatous polyps; CD, Crohnʹs disease; CRC, colon cancer; E, enteritis; 1C, ischemic colitis; U, ulcers; UC, ulcerative colitis.

Figure 1 Schematic view illustrating how a specific matrix metalloproteinase (MMP) (eg, MMP-3 [A]) triggers the conversion of other MMP zymogens (proMMP-7 [B], proMMP-9 [C], or proMMP-13 [D]) to their active forms.

Figure 2 Schematic view of situations in which MMP is either controlled or not by tissue inhibitors of MMPs (TIMPs). (A) In physiological conditions, TIMPs form with MMPs reversible complexes in a 1:1 ratio thereby controlling MMP activity. Within inflammatory microenvironment, the TIMP/MMP ratio can be decreased by overexpression of MMPs without a parallel increase of TIMPs (B), a sudden decrease in the expression of TIMPs (C) or increased MMP concentration that is accompanied by concomitant decrease in TIMP levels (D).

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