基质金属蛋白酶-1和金属蛋白酶组织抑制剂-1在溃疡性结肠炎中的表达
Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis.
作者信息
Wang Ying-De, Yan Pei-Yun
机构信息
Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
出版信息
World J Gastroenterol. 2006 Oct 7;12(37):6050-3. doi: 10.3748/wjg.v12.i37.6050.
AIM
To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcerative colitis (UC).
METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and controls. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the severity of clinical symptoms of the patients with UC were also analyzed.
RESULTS
The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was significantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically significant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA expression of MMP-1 and TIMP-1 in ulcerated colonic mucosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analysis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).
CONCLUSION
Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC patients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.
目的
检测溃疡性结肠炎（UC）患者结肠黏膜中金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）的表达。
方法
采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，研究UC患者及对照组中MMP-1和TIMP-1在mRNA和蛋白水平的表达。同时分析MMP-1 mRNA、TIMP-1 mRNA、MMP-1 mRNA/TIMP-1 mRNA比值与UC患者临床症状严重程度之间的关系。
结果
溃疡和炎症结肠黏膜中MMP-1 mRNA和TIMP-1 mRNA的表达显著高于非炎症结肠黏膜（P < 0.001），但UC患者非炎症结肠黏膜与正常对照组之间无统计学差异（P > 0.05）。与正常对照组相比，UC患者溃疡结肠黏膜中MMP-1和TIMP-1的mRNA表达分别增加了80倍和2.2倍。在炎症结肠黏膜中，增加倍数分别为30倍和1.6倍。免疫组织化学分析显示，在UC患者的溃疡、炎症和非炎症结肠黏膜以及正常对照组中，MMP-1表达的阳性率分别为87%、87%、40%和35%，TIMP-1表达的阳性率分别为89%、89%、80%和75%。此外，MMP-1 mRNA、TIMP-1 mRNA表达及MMP-1 mRNA/TIMP-1 mRNA比值与临床症状严重程度相关（P <0.05）。
结论
病变结肠黏膜中MMP-1的过度表达导致UC患者细胞外基质（ECM）过度水解和溃疡形成。MMP-1 mRNA、TIMP-1 mRNA及MMP-1 mRNA/TIMP-1 mRNA比值可作为判断UC患者临床症状严重程度的生物标志物。外源性TIMP-1或MMP-1抑制剂治疗是UC患者的一种新治疗方法。
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