Increased concentration of tissue-degrading matrix metalloproteinases and their inhibitor in complicated diverticular disease.
OBJECTIVE
Complicated diverticular disease is associated with extensive structural changes of the colonic wall. Turnover of extracellular matrix (ECM) plays a pivotal role in this process. Proteolytic enzymes, including matrix metalloproteinases (MMPs), are capable of degrading most components of ECM. Their activity is regulated by inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Disturbances of the MMP-TIMP balance can cause tissue degradation or fibrosis. The aim of this study was to assess the concentration and distribution of MMPs and TIMPs in colonic biopsies.


METHODS
Twenty-seven patients who had undergone sigmoid colectomy were included in the study. Full-thickness biopsies from affected and non-affected parts of each resected specimen were collected. Expressions of the proteins MMP-1, -2, -3, -9, TIMP-1 and TIMP-2 were quantified by ELISA and localized by immunohistochemistry.


RESULTS
The concentrations of MMP-1, MMP-2 and TIMP-1 were significantly higher in affected tissue than concentrations in non-affected tissue (MMP-1 p=0.005, MMP-2 p=0.0003 and TIMP-1 p<0.0001). In affected segments in general, there was an increased expression in the entire bowel wall, predominantly for MMP-2, MMP-3 and TIMP-1.


CONCLUSIONS
Concentrations of MMP-1, MMP-2 and TIMP-1 were increased in intestinal segments affected by complicated diverticular disease and distributed throughout the entire bowel wall, which may explain the structural changes.
Rosemar
Anders
A
Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, Gothenburg, Sweden. anders.rosemar@surgery.gu.se
Ivarsson
Marie-Louise
ML
Börjesson
Lars
L
Holmdahl
Lena
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003106:Colon / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004239:Diverticulitis, Colonic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases