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


CONCLUSIONS
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.
Wang
Ying-De
YD
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China. albertwyd@yahoo.com.cn
Mao
Jing-Wei
JW
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1