Baba Haruna, Ohtsuka Yoshikazu, Fujii Tohru, Haruna Hidenori, Nagata Satoru, Kobayashi Hiroyuki, Yamataka Atsuyuki, Shimizu Toshiaki, Miyano Takeshi, Yamashiro Yuichiro
Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Pediatr Surg Int. 2009 Feb;25(2):157-62. doi: 10.1007/s00383-008-2311-9. Epub 2008 Dec 17.
Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have been implicated in tissue injury and remodeling in many organs. The objective of this study was to evaluate the expression of MMP-3 and -9, and TIMP-1, -2, and -3 and their relationship to liver fibrosis in infants with biliary atresia.
The expression of MMP-3 and-9 and TIMP-1, -2 and -3 was investigated in liver tissue samples of nine patients with biliary atresia. In addition, the expression of CCR-4 and CCR-5 was analyzed to investigate the activation of Th1 and Th2 cells. The mRNA levels were measured by semiquantitative reverse transcriptase polymerase chain reaction.
The expression of MMP-3 was higher than that of MMP-9 in all samples (P < 0.01). The expression of TIMP-1 was higher than that of TIMP-2 and -3 in all samples (P < 0.01). The expression of CCR-5 was higher than that of CCR-4 (P < 0.05), which implied higher activation of Th1 cells relative to Th2 cells.
Our findings suggest that MMP-3, possibly induced by Th1 cytokines, and its balance with TIMP-1, may be one of the factors involved in the pathogenesis of biliary atresia.
基质金属蛋白酶（MMPs）及其内源性组织抑制剂[金属蛋白酶组织抑制剂（TIMPs）]与许多器官的组织损伤和重塑有关。本研究的目的是评估胆道闭锁婴儿中MMP-3、-9以及TIMP-1、-2和-3的表达及其与肝纤维化的关系。
研究了9例胆道闭锁患者肝组织样本中MMP-3、-9以及TIMP-1、-2和-3的表达。此外，分析了CCR-4和CCR-5的表达以研究Th1和Th2细胞的活化情况。通过半定量逆转录聚合酶链反应测量mRNA水平。
所有样本中MMP-3的表达均高于MMP-9（P<0.01）。所有样本中TIMP-1的表达均高于TIMP-2和-3（P<0.01）。CCR-5的表达高于CCR-4（P<0.05），这意味着Th1细胞相对于Th2细胞具有更高的活化程度。
我们的研究结果表明，可能由Th1细胞因子诱导的MMP-3及其与TIMP-1的平衡，可能是参与胆道闭锁发病机制的因素之一。
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