Matrix metalloproteinases as potential fecal biomarkers for ulcerative colitis – a function beyond their proteolytic activity

Figures & data

Figure 1 A schematic presentation of MMPs active during UC and in the normal colonic tissue.

Notes: The schematic shows immune cells (neutrophils, T-cells, macrophages), myofibroblasts, and epithelial cells as the sources of different MMPs active during UC and in the normal colonic tissue. It indicates an increase in the infiltration of immune cells and myofibroblasts through the epithelial–mucosal barrier, via leaky tight junctions during UC.
Abbreviations: MMP, matrix metalloproteinase; UC, ulcerative colitis; TJ, tight junction; M, MMP.

Table 1 The comparative analysis of MMPs (also active in UC) as different body-fluid biomarkers

Name of MMPs	Mechanistic role in intestinal inflammation	Established biomarker activity in different malignancies
		Serum	Urine	Blood	Feces	CSF
MMPI (collagenase 1)	Cleaves TNFα, MCP.	–	+^Citation39	+^Citation38	–	–
MMP2 (gelatinase A)	Cleaves endothelin-1 to a peptide that binds to endothelin receptor signaling the upregulation of CD11/CD18 on neutrophil surfaces via MAPK pathways. Triggers the leukocyte adhesion and neutrophil trafficking to inflamed tissues.
MMP3 (stromelysin-I)	Activates TGF-β. Regulates chemokine signaling by facilitating the cleavage of MCP1, MCP2, MCP3, and MCP4. Inhibition of leukocyte invasion is unknown, indicating the less pronounced anti-inflammatory effect.	+^Citation43		+^Citation49
MMP7 (matrilysin)	Cleaves TNFα. Aids the growth of myofibroblasts that may take part in maintaining the mucosal homeostasis. Overexpression may delay epithelial wound healing.	+^Citation57	+^Citation56	+^Citation48,Citation55	+^Citation59
MMP9 (gelatinase B)	Activates proinflammatory cytokines such as IL-1, TGF-β, and TNFα. Involved with the migration of T lymphocytes, leukocyte invasion, and transendothelial migration to regulate inflammation. Cleaves chemokines such as IL-8, GCP-2, and ENA-78. Degrades BM facilitating lymphocytes and neutrophil migration to the inflammatory site.	+^Citation67–Citation69	+^Citation70	+^Citation27	+^Citation71
MMP10 (stromelysin-2)	Mechanism not yet known.	–	+^Citation39	–	–	+^Citation73
MMP12	Mechanism not yet known.	–	–	–	–	–
MMP14 (membrane type 1 MMP)	Cleaves proinflammatory cytokines TNFα and TGF-β. Cleaves chemokine MCP3.	+^Citation80		+^Citation27

Abbreviations: MMP, matrix metalloproteinase; UC, ulcerative colitis; CSF, cerebrospinal fluid; TNFα, tumor necrosis factor alpha; MCP, monocyte chemoattractant protein; MAPK, mitogen-activated protein kinase; TGF-β, transforming growth factor β; IL-1, interleukin-1; IL-8, interleukin-8; GCP-2, granulocyte chemotactic protein 2; ENA-78, epithelial cell-derived neutrophil-activating peptide 78; BM, basement membrane; –, not known or not available.

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