Liver-Specific Overexpression of igf-2 Leads to Liver hypertrophy
Date Issued
2005
Date
2005
Author(s)
Chen, Yu-Da
DOI
zh-TW
Abstract
Abstract
Insulin-like growth factor-2 (IGF-II), mainly synthesized in liver then transport to target tissues through endocrine system, is an important factor that stimulate cell proliferation, differentiation and division, promote organ development and play as a survival factor in apoptosis. However, the functional role of liver-derived IGF-II before partum still remains unclear. In this study, we use liver fatty acid binding protein (L-FABP) promoter to drive IGF-II expression in a liver-specific manner. To facilitate the direct imaging of liver development, constructs containing expression cascade were introduced to one-cell stage embryo of transgenic zebrafish lines bearing liver-specific GFP expression. Exogenous IGF-2 expression is first detected at 34hpf under the control of LFABP promoter. Obvious liver enlargement was observed at 10dpf and continues to grow; gut tube was pushed up by the enlarged liver but appears un-disrupted morphologically. At 17dpf, the volume of IGF-2 over-expressed liver is 1.5 times bigger statistically than the wild-type control using confocal microscopy. The increased number and enlarged hepatocyte cell shape were also observed under confocal microscopy examination. We further use PT-PCR to monitor molecular, which may involve in this phenomena. IGF-binding protein, IGFBP1 and IGFBP3 were down-regulated; Cell cycle related gene such as c-myc, cyclin-D1, gankyrin; anti-apoptosis genes such as bcl-xl and liver-enriched transcription factors such as HNF4αand HNF1αwere up-regulated suggesting the rapid cell division leading to increase cell number were controlled by hepatic program and anti-apoptosis genes.
Subjects
第二型類胰島素因子
肝癌
igf-2
Liver hypertrophy
Type
other