Synergistic induction by collagen and fibronectin of liver-specific genes in rat primary cultured hepatocytes.
The extracellular matrix plays an important role for maintaining liver functions. We examined the effects of type I collagen and fibronectin on the expression of liver-specific genes in rat primary hepatocytes. When primary culture hepatocytes were overlaid with a type I collagen-gel, the expression of liver-specific genes (tyrosine aminotransferase, aldolase B, and albumin) increased by 4-5 times, compared with not overlaid hepatocytes. In contrast, the expression of non-liver-specific genes (GAPDH and beta-actin) was suppressed under the same conditions. The addition of fibronectin together with type I collagen-gel further enhanced the expression of liver-specific genes by 1.4-1.8 times. The addition of GRGDS peptide instead of fibronectin with the collagen-gel had a similar effect on hepatic gene expression to that of fibronectin. Addition of fibronectin alone exhibited had no effect on gene expression. These results suggest that type I collagen and fibronectin synergistically induce liver-specific genes.
Ouchi
H
H
Department of Biochemistry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
Otsu
K
K
Kuzumaki
T
T
Iuchi
Y
Y
Ishikawa
K
K
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D004357:Drug Synergism; D005353:Fibronectins / Q000494:pharmacology*; D005782:Gels; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D005782:Gels; D009842:Oligopeptides; D003094:Collagen; C049554:glycyl-arginyl-glycyl-aspartyl-serine