Expression of matrix metalloproteinase-1 and tumor necrosis factor-alpha in ulcerative colitis

World J Gastroenterol. 2007 Nov 28;13(44):5926-32. doi: 10.3748/wjg.v13.i44.5926.

Abstract

Aim: To examine the expression of matrix metallo-proteinase-1 (MMP-1) and tumor necrosis factor-alpha (TNF-alpha) in the colon mucosa of patients with ulcerative colitis (UC).

Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to examine the expression of MMP-1 and TNF-alpha at both mRNA and protein levels in the colon mucosa of patients with UC. Correlation between MMP-1 and TNF-alpha and their correlation with the severity of the disease were also analyzed statistically.

Results: The expression of MMP-1 and TNF-alpha in the ulcerated and inflamed colon mucosa of patients with UC was significantly higher than that in the non-inflamed mucosa of normal controls at both mRNA and protein levels. Furthermore, the expression of MMP-1 and TNF-alpha in the ulcerated area was significantly higher than that in the inflamed area of patients with UC (0.9797 +/- 0.1433 vs 0.6746 +/- 0.0373, 0.8669 +/- 0.0746 vs 0.5227 +/- 0.0435, P < 0.05). There was no statistically significant difference in the non-inflamed area of normal controls. There was a significant correlation between MMP-1 and TNF-alpha expression (0.9797 +/- 0.1433 vs 0.8669 +/- 0.0746, P < 0.05), the correlating factor was 0.877. MMP-1 and TNF-alpha showed a significant correlation with the severity of the disease (0.0915 +/- 0.0044 vs 0.0749 +/- 0.0032 , 0.0932 +/- 0.0019 vs 0.0724 +/- 0.0043, P < 0.05), their correlating factors were 0.942 and 0.890, respectively.

Conclusion: Excessively expressed MMP-1 directly damages the colon mucosa by degrading extracellular matrix (ECM) in patients with UC. While damaging colon mucosa, excessively expressed TNF-alpha stimulates MMPs secreting cells to produce more MMP-1 and aggravates the mucosa damage. MMP-1 promotes secretion of TNF-alpha in a positive feedback manner to cause further injury in the colon mucosa. MMP-1 and TNF-alpha correlate well with the severity of the disease, and therefore, can be used clinically as biological markers to judge the severity of UC.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Case-Control Studies
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Colon / metabolism
  • Colon / pathology
  • Female
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Matrix Metalloproteinase 1 / metabolism*
  • Middle Aged
  • RNA, Messenger / metabolism
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Biomarkers
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 1