Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats
Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats
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DOI：
10.1016/j.bbrc.2007.03.035
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发表时间：
2007-05-11
影响因子：
3.1
通讯作者：
Tsubouchi, Hirohito
中科院分区：
文献类型：
--
作者：
Abe, Hiroo;Uto, Hirofumi;Tsubouchi, Hirohito
骨激活素（OA）在肝纤维化中的作用仍不清楚。用缺乏胆碱、L-氨基酸限定 (CDAA) 饮食喂养野生型 (WT) 和 OA 转基因 (OA-Tg) 大鼠 12 周后，我们评估了肝纤维化。与 WT 大鼠相比，OA-Tg 大鼠的肝纤维化和 cc-平滑肌肌动蛋白的表达减少。我们通过微阵列分析检查了 31,100 个基因的表达，发现 OA-Tg 大鼠肝脏中有 177 个和 256 个基因分别上调和下调，与 WT 大鼠肝脏相比，上调和下调至少两倍。在这些基因中，我们证实 OA-Tg 大鼠肝脏中金属蛋白酶-1 和 -2 组织抑制剂、I 型胶原以及血小板衍生生长因子受体-α 和 -β 的表达水平显着下调。这些结果表明，转基因OA表达减弱了肝纤维化的发展，这与抑制参与其发病机制的特定基因有关。 (c) 2007 Elsevier Inc. 保留所有权利。
The role of osteoactivin (OA) in liver fibrogenesis remains unclear. After feeding wild-type (WT) and OA transgenic (OA-Tg) rats a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks, we evaluated liver fibrosis. Hepatic fibrosis and expression of cc-smooth muscle actin protein in OA-Tg rats were reduced in comparison to WT rats. Our examination of the expression of 31,100 genes by microarray analysis identified 177 and 256 genes that were upregulated and downregulated, respectively, by at least twofold in OA-Tg rat livers in comparison to WT rat livers. Of these genes, we confirmed a significant downregulation in the expression levels of tissue inhibitor of metalloproteinase-1 and -2, type I collagen, and platelet-derived growth factor receptor-alpha and -beta in the livers of OA-Tg rats. These results indicate that transgenic OA expression attenuates the development of hepatic fibrosis in association with the suppression of specific genes involved in its pathogenesis. (c) 2007 Elsevier Inc. All rights reserved.