Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.

Influence of hepatic arterial blockage on blood perfusion and VEGF,MMP-1 expression of implanted lver cancer in rats

AIM: To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P【0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P【0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P【0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P【0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P【0.01). CONCLUSION: Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major cause of up-regulated expression of VEGF.

Dynamic changes in the collagen metabolism of liver fibrosis at the transcription level in rabbits with Schistosomiasis japonica

OBJECTIVE: To study the role of the synthesis and degradation of collagen at the transcription level during liver fibrogenesis due to schistosomiasis japonica in rabbits. METHODS: New Zealand rabbits challenged by cercariae of Schistosoma japonicum (S. japonicum) were served as animal models for liver fibrosis. Liver specimens were collected through operations at 4, 6, 8, 10, 12, 16, 20, 24 and 28 wks after challenge. Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels of liver tissue were detected by RT-PCR + Dot blot. The size of egg granulomas and the degree of liver fibrosis were measured by histopathological examinations. RESULTS: Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased simultaneously in the early stage after challenge. Most of them reached their peak at 10 weeks, and compared with normal controls, type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased by 12.0-, 11.0-, 6.6-, 10.0- and 11.0-fold, respectively, coinciding with the change of egg granulomas, i.e., the change in the inflammatory process. Then both collagen and collagenase mRNA levels decreased. Type I, III and IV collagen mRNA levels declined to 2-fold to 3-fold as compared with normal controls (P 0.05) at 28 wks. This study shows that the synthesis and degradation of collagen keep a dynamic balance at the early stage of schistosomiasis japonica challenge, while at the later stages the quantity of collagen synthesis was higher than that of collagen degradation. CONCLUSIONS: It was confirmed at transcription level that when the quantity of collagen synthesis was higher than that of collagen degradation liver fibrogenesis may be resulted in.