Activation of Proalpha2(I) collagen promoter during hepatic fibrogenesis in transgenic mice.
We previously identified the promoter sequence that is essential for basal and TGF-beta-stimulated transcription of alpha2(I) collagen gene (COL1A2). In the present study, we examined whether the promoter is activated during hepatic fibrogenesis by utilizing transgenic mice harboring the COL1A2 upstream sequence. Intraperitoneal CCl4 administration activated the -17 kb COL1A2 promoter more than 10-fold, whereas partial hepatectomy resulted in no significant change in the promoter activity. The non-parenchymal cell fraction, but not parenchymal hepatocytes, isolated from mice harboring the -313 COL1A2 promoter linked to a beta-galactosidase reporter gene contained large amounts of beta-galactosidase and endogenous COL1A2 mRNAs. beta-galactosidase activity in the cells from CCl4-treated mice was significantly higher than in those from untreated animals. These results indicated that different molecular mechanisms control COL1A2 transcription in CCl4-induced liver injury/fibrosis and physiological regeneration after partial hepatectomy, and that the -313 COL1A2 promoter is activated in a cell type-specific manner during hepatic fibrogenesis.
Department of Internal Medicine and Clinical Research Institute, National Kanazawa Hospital, Kanazawa, Japan. Yutakai@po.incl.or.jp
Y
Y
Inagaki
S
S
Truter
G
G
Bou-Gharios
L A
LA
Garrett
B
B
de Crombrugghe
T
T
Nemoto
P
P
Greenwel
D000818:Animals; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008106:Liver Cirrhosis, Experimental / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
D011498:Protein Precursors; D016212:Transforming Growth Factor beta; C108197:alpha-precollagenous protein, Mytilus edulis; D003094:Collagen