title: Differential expression and processing of matrix metalloproteinase 19 marks progression of gastrointestinal diseases.
abstract: Matrix metalloproteinases (MMPs), responsible for extracellular matrix remodelling and processing of numerous soluble and cell-surface proteins, appear to play important roles in pathogenesis of gastrointestinal diseases. MMPs influence migration of inflammatory cells, mucosal destruction, matrix deposition and degradation. In this study, we analysed the expression of MMP-19 in the main forms of gastrointestinal diseases including inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, and colorectal carcinoma. We identified prominent MMP-19 expression in unaffected areas of intestinal epithelia and macrophages but not in other cells or tissues. Abundant expression of MMP-19 was also found in the endothelium of blood and lymphatic vessels of inflamed intestinal tissue. High MMP-19 immunoreactivity was also associated with macrophages in inflamed areas and myenteric plexuses. In comparison to the intestinal epithelium, all these cell types and compartments appeared to express MMP-19 irrespective of the disease pathogenesis and progression. Intestinal epithelia exhibited striking differential immunoreactivity for MMP-19. While immunoreactivity of monoclonal antibody recognizing the propeptide domain declined in virtually all IBD and colorectal carcinoma samples, other polyclonal antibodies against the hinge region and propetide domain did not show such an obvious decrease. Additional Western blotting analysis revealed that the antibodies against MMP-19 recognize differently processed forms of this MMP. The disappearance of immunoreactivity of the monoclonal anti-propeptide domain antibody does not mean down-regulation of MMP-19, but processing of the immature form. As this processing likely leads to the activation of this MMP, the differential staining pattern may be an important sign of disease progression.
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: M
authors: M
authors: Cervinková
authors: Department of Surgery, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic.
authors: P
authors: P
authors: Horák
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: I
authors: I
authors: Kanchev
authors: Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague, Czech Republic.
authors: R
authors: R
authors: Matěj
authors: Department of Surgery, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic.
authors: J
authors: J
authors: Fanta
authors: Gastroenterology Surgical Centre, Hospital of Merciful Sisters of St. Borromeo, Prague, Czech Republic.
authors: R
authors: R
authors: Sequens
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: P
authors: P
authors: Kašpárek
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: L
authors: L
authors: Sarnová
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: J
authors: J
authors: Turečková
authors: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic.
authors: R
authors: R
authors: Sedláček
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005767:Gastrointestinal Diseases / Q000201:enzymology* / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000906:Antibodies; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19