Increased distribution of collagen type III and reduced expression of matrix metalloproteinase 1 in patients with diverticular disease.
ABSTRACT Diverticular disease is an increasingly common clinical problem especially in Western industrialized countries, but the mechanism by which the disease develops remains unclear. Based on studies showing a structural change in the colonic wall in these patients, we examined whether there are any disorders concerning the collagen metabolism in patients with diverticular disease. Samples of colonic tissue from 13 patients with diverticulitis were compared to 14 controls. We performed a Sirius red test for the overall collagen content and immunohistochemical studies facing differentiation between collagen type I and type III and the expression of matrix metalloproteinases 1 and 13. In the bowel sections of patients with diverticulitis there were decreased levels of mature collagen type I (1.37+/- 0.32 vs. 1.59 +/- 0.31) and increased levels of collagen type III (1.61+/- 0.32 vs. 1.42 +/- 0.42), with a resulting lower collagen ratio I/III. The expression of MMP-I was reduced significantly in the diverticulitis group (4.83 +/- 0.92 vs. 6.02 +/- 1.98) while expression of MMP-13 did not differ significantly between the two groups (1.03 +/- 0.11 vs. 1.04 +/- 0.12). Our findings support the theory of structural changes in the colonic wall as one of the major pathogenic factors in the development of diverticular disease. Further studies must focus on the complex interactions of several extracellular matrix components.
SourceAvailable from: Winfried Häuser
Article: Z Gastroenterol. 2014 Jul;52(7):663-710. doi: 10.1055/s-0034-1366692. Epub 2014 Jul 15. [S2k guidelines diverticular disease/diverticulitis]. [Article in German] Leifeld L, Germer CT, Böhm S, Dumoulin FL, Häuser W, Kreis M, Labenz J, Lembcke B, Post S, Reinshagen M, Ritz JP, Sauerbruch T, Wedel T, von Rahden B, Kruis W.Zeitschrift für Gastroenterologie 07/2014; 52(7):663. DOI:10.1055/s-0034-1366692 · 1.67 Impact Factor
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ABSTRACT: Colon healing and remodeling depends on the collagen changes in extracellular matrix. Some conditions, disrupt its turnover, causing strength weakening of the scar, as a result of high activity of local matrix metalloproteinases, causing a high risk of dehiscence. The extracellular matrix metalloproteinases are a family of zinc-dependent endopeptidases, or metzincines, and have been currently recognized in humans about 24 genes responsible for each one. The first MMP, colagenase (MMP-1), was described by Gross and Lapière (1962), while studying tadpole resorption of the American bullfrog. Metalloproteinases activity in cancer research, has taken a special place. Currently, evidences points to the cancer cell ability to interfere with enzymatic activity modulation - an co-factor which affects local invasiveness and metastatic dissemination. Both MMPs-2 and -7 have been frequently observed in colon cancer. Moreover, MMP-12 seems to counteract MMP-7 effect therefore considered as a protector and associated with better prognosis, in contrast to MMP-3, which may be responsible for a worse outcome. Association between high activity of MMPs, the prognosis of cancer and increased risk of intestinal anastomotic leakage has been highlighted, suggesting a consistent trilogy. Pharmacological therapy using MMPs inhibitors has been extensively studied, especially targeted for cancer control. The article discusses the most relevant information and updated information on the subject.Revista Brasileira de Coloproctologia 06/2010; 30(2):141-151. DOI:10.1590/S0101-98802010000200004
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ABSTRACT: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. A role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders, youthful onset in some patients, and the observation of families with multiple affected individuals. The TNFSF15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis (UC), aggressive Crohn's disease (CD), and pouchitis after restorative proctocolectomy. In the discovery phase of this study, 21 sporadic surgical diverticulitis (SD) patients (9 female, mean age = 52 ± 5) and 5 individuals from a single family with surgically managed diverticulitis [familial diverticulitis (FD), 4 female, mean age = 51.1 ± 7] were studied. SD patients were age and sex matched with 3 separate groups of healthy, CD and UC control patients. All patients were genotyped for 5 known TNFSF15-associated SNPs. The SNP discovered to be associated with diverticulitis (rs7848647) was then confirmed in a separate test group composed of 34 additional patients (20 female, mean age 57.7 ± 2) who also underwent surgical treatment for diverticulitis. These patients were age matched to a new control cohort of patients having no history of diverticulitis (26 female). Patients were genotyped using a TaqMan assay. In the discovery phase, logistical regression on matched subjects was performed to determine an association of TNFSF SNP with diverticulitis versus the control groups. In the test phase, significance for the rs7848647 SNP was assessed by the Fischer's exact test. In the discovery phase, the TNFSF15 SNP rs7848647 was significantly associated with SD (p = 0.0003) versus all control groups studied. The risk allele for this SNP (G substituted for A) was found in all SD patients. The homozygous GG allele was found in 62% (13/21) of SD patients versus only 5% (1/21) of healthy controls (p = 0.001) and 24% (10/42) of all UC + CD controls (p = 0.002). All 5 members of the FD cohort were homozygous for the at-risk "G" allele. In the test group, the homozygous GG genotype was found in 56% of SD patients compared with 17% of healthy controls (p = 0.006). Risk of SD seemed to increase with number of the G alleles with 8% of SD patients having AA homozygosity, 35% of SD patients having AG heterozygosity, and 56% of SD patients having GG homozygosity. The SNP rs7848647 associated with the TNFSF15 gene is associated with surgical diverticulitis. This finding suggests a fundamental role for TNFSF15, a T-cell receptor gene involved in T-cell maturation, in the pathophysiology of diverticulitis requiring surgery. This SNP may be a marker of diverticular disease severity that might assist in surgical decision making.Annals of surgery 06/2014; 259(6):1132-7. DOI:10.1097/SLA.0000000000000232 · 7.19 Impact Factor