Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats

被引:42
作者
Abe, Hiroo
Uto, Hirofumi
Takami, Yoichiro
Takahama, Yuka
Hasuike, Satoru
Kodama, Mayumi
Nagata, Kenji
Moriuchi, Akihiro
Numata, Masatsugu
Ido, Akio
Tsubouchi, Hirohito [1 ]
机构
[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest & Lifestyle Related Dis, Kagoshima 890, Japan
[2] Miyazaki Univ, Fac Med, Miyazaki, Japan
[3] Miyazaki Prefectural Ind Support Fdn, Miyazaki, Japan
[4] Kyoto Univ Hosp, Translat Res Ctr, Dept Expt Therapeut, Kyoto 606, Japan
基金
日本科学技术振兴机构;
关键词
osteoactivin; choline-deficient L-amino acid-defined diet; hepatic fibrosis; TIMP; PDGF receptor;
D O I
10.1016/j.bbrc.2007.03.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
引用
收藏
页码:610 / 615
页数:6
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