Correlation Study Of Colonic Tissue And Plasma MMP-1 And TIMP-1 Expression In Patients With Ulcerative Colitis

Objective: This study was aimed to examine the expression of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in colonic mucosa and in plasma of patients with ulcerative colitis (UC)at the level of mRNA and protein, to investigate the correlation of MMP-1 and TIMP-1 expressed in colonic mucosa and plasma, to analyze their relationships with the severity of clinical symptoms, and to identify whether or not MMP-1 and TIMP-1 expressed in plasma could be used as new, simple and useful biological parameters in diagnosing UC.Methods: Colonic mucosa and venous blood samples were collected from thirty patients with UC who were classified into two groups: mild and moderate to severe groups according to the clinical symptoms and pathological histology. Meanwhile, specimens from colonic mucosa and plasma in fifteen normal persons were also collected as controls. RT-PCR and immunohistochemistry were used to examine the expression of MMP-1 and TIMP-1 at the level of mRNA and protein. ELISA assay was used to measure their plasma levels. Statistical analysis was carried out to investigate the correlations of MMP-1 and TIMP-1 between the colonic mucosa and plasma and their relationships with the severity of clinical symptoms of the patients.Results:1.The expression of MMP-1 and TIMP-1 in the colonic mucosa of patients with UC at the level of mRNA and protein was significantly higher than that in controls, and there is a positive correlation between the expression of MMP-1 and TIMP-1 and the severity of clinical symptoms (P<0.05) . 2. The plasma level of MMP-1 and TIMP-1 was significantly higher than that in controls. Expression of TIMP-1 was correlated well with the severity of clinical symptoms (P<0.05), and expression of MMP-1 in moderate to severe group was significantly higher than that in controls (P<0.05), but no significant difference was found between mild and control groups (P>0.05).3. There was a significant correlation of MMP-1 between colonic mucosa and plasma (P<0.05), the correlating factor was 0.805, but was not linear correlation (P=0.282);there was also a significant correlation of TIMP-1 between colonic mucosa and plasma (P< 0.05), the correlating factor was 0.908, but was not linear correlation neither (P=0.062).4. In colonic tissue and plasma, there was significant correlation between the expression of MMP-1 and TIMP-1 , the correlating factors were 0.986 and 0.914, respectively; the colonic and plasma TIMP-1 were both correlated with the severity of clinical symptoms (P < 0.05), their correlating factors were 0.822 and 0.658, respectively; the expression of MMP-1 and MMP-1/TIMP-1 ratio was significantly correlated with the severity of clinical symptoms in the colonic tissue (P < 0.05), the correlating factors were 0.926 and 0.678, respectively, but the plasma MMP-1 and MMP-1/TIMP-1 ratio were not (P>0.05).Conclusions: 1.A positive, but un-linear correlation of MMP-1 and TIMP-1 expression existed between colonic mucosa and plasma, indicating that plasma MMP-1 and TIMP-1 could reflect their expression in the colonic tissue.2. The expression of TIMP-1 in colonic mucosa and plasma and of MMP-1 in colonic mucosa was significantly correlated with the severity of clinical symptoms, but the plasma MMP-1 was only significantly increased in moderate to severe group.3. The plasma MMP-1 and TIMP-1, especially TIMP-1, could be used as new, simple and useful biological parameters in the clinical diagnosis of UC.