Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats.
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 alpha-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.
Abe
Hiroo
H
Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Uto
Hirofumi
H
Takami
Yoichiro
Y
Takahama
Yuka
Y
Hasuike
Satoru
S
Kodama
Mayumi
M
Nagata
Kenji
K
Moriuchi
Akihiro
A
Numata
Masatsugu
M
Ido
Akio
A
Tsubouchi
Hirohito
H
D000818:Animals; D030801:Animals, Genetically Modified; D002796:Choline Deficiency / Q000378:metabolism; D020869:Gene Expression Profiling; D015316:Genetic Therapy; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
C503043:Gpnmb protein, rat; D008562:Membrane Glycoproteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D020796:Receptor, Platelet-Derived Growth Factor alpha