The Expressions Of Matrix Metalloproteinase-1 (MMP-1) And Tissue Inhibitor Of Metalloproteinase-1 (TIMP-1) In Ulcerative Colitis

Objective:This study was aimed to examine the expressions of MMP-1 and TIMP-1 in colon mucosa of patients with ulcerative colitis, and to investigate the roles of MMP-1,TIMP-1 in the process of ulcerative formation and reparation in ulcerative colitis,and the relationships between the ratio of MMP-1/TIMP-1,MMP-1,TIMP-1 and the degree of clinical symptom of the patients with ulcerative colitis, so as to primarily make sure the roles of MMP-1,TIMP-1,the ratio of MMP-1/TIMP-1 in ulcerative colitis,and whether MMP-1,TIMP-1,the ratio of MMP-1/TIMP-1 could be used as biomarkers to judge the degree of clinical symptom of the patients with ulcerative colitis. Methods:Thirty patients with ulcerative colitis were collected ,and were graded according to the clinical symptom and pathologic histology: mild,moderate,severe. The biopsy specimens were taken from areas of ulcerated, inflamed and non-inflamed colonic mucoma. Meanwhile,we collected twenty biopsy specimens of normal persons as controls.RT-PCR and immunohistochemistry were used to study the expressions of MMP-1,TIMP-1 at the level of mRNA and protein,and the relationships between MMP-1,TIMP-1,MMP-1/TIMP-1 and the degree of clinical symptom of the patients with ulcerative colitis was analyzed by statistical methods. Results:The mRNA expressions of MMP-1 and TIMP-1 in the ulcerated and inflamed colonic mucoma were significantly higher than those of non-inflamed colonic mucoma (P<0.001)and the control(P<0.001).The ratios of IOD between MMP-1,TIMP-1 and β-actin in ulcerated tissue samples were increased 80-fold and 2.2-fold compared with those of the control. And those were 30-fold and 1.6-fold in inflamed colonic mucoma. The expressions of MMP-1,TIMP-1 at the protein level in the ulcerated and inflamed colonic mucoma were significantly increased than those of non-inflamed colonic mucoma(P<0.05)and the control(P<0.05). Either at the mRNA level or at the protein level the expressions of MMP-1 were no statistically significant in non-inflamed colonic mucosa compared with the control. Among the ulcerated , inflamed , non-inflamed colonic mucoma and the control,the positive rates of MMP-1 expressions were 87%,87%,40% and 35% respectively, and those of TIMP-1 were 89%,89%,80% and 75%.Furthermore, the expressions of MMP-1 were well related to those of TIMP-1(P<0.001),and correlating factor, r was 0.801.The expressions of MMP-1,TIMP-1 and the ratio of MMP-1/ TIMP-1 were related to the degree of clinical symptom (P<0.05), and correlating factor, r was 0.328,0.552,0.411,respectively。Conclusions:The increased expressions of MMP-1 and the comparatively deficient expressions of TIMP-1 are related to tissue damage in ulcerative colitis.The ratio of MMP-1 and TIMP-1 is off balance in ulcerative colitis and it is very important in the process of tissue damage. MMP-1,TIMP-1 and the ratio of MMP-1/TIMP-1 could be used as biomarkers to judge the degree of clinical symptom of the patients with ulcerative colitis;Either substitute treatment using exogenous TIMP-1 or treatment with MMPs inhibitors might be a new way in treating ulcerative colitis.