| 15070850 |
Scharf JG, Dombrowski F, Novosyadlyy R, Eisenbach C, Demori I, Kubler B, Braulke T: Insulin-like growth factor (IGF)-binding protein-1 is highly induced during acute carbon tetrachloride liver injury and potentiates the IGF-I-stimulated activation of rat hepatic stellate cells. Endocrinology. 2004 Jul;145(7):3463-72. Epub 2004 Apr 7.
Hepatic stellate cells (HSC) play a pivotal role in hepatic tissue repair and fibrogenesis. IGF-I has been considered a mitogenic signal for activation and proliferation of HSC in vitro. In the present study IGF-I and IGF-binding protein (IGFBP) gene expression was studied in a model of acute liver injury induced by a single intragastric dose of carbon tetrachloride (CCl (4)) in adult rats. Northern blot analysis revealed a marked increase in IGFBP-1 mRNA levels, with a maximum between 3 and 9 h after CCl (4) application, whereas steady state mRNA levels of IGF-I were only moderately altered. In situ hybridization experiments demonstrated that this increase in IGFBP-1 mRNA was due to a strong expression of IGFBP-1 in the perivenous region 6-12 h after CCl (4) application, extending to the midzonal region of the acinus within 24-48 h. Consequently, a prominent immunostaining for IGFBP-1 was observed in perivenous areas, with a maximum 24-48 h after intoxication. Preincubation of early cultured HSC with a nonphosphorylated IGFBP-1 from human amniotic fluid resulted in a 3.4-fold increase in IGF-I-induced DNA synthesis. The mitogenic effect of IGF-I was also potentiated when HSC were cocultivated with IGFBP-1-overexpressing BHK-21 cells compared with nontransfected cells. These data suggest that IGFBP-1 released during the early steps of liver tissue damage and repair may interact with HSC and potentiate the sensitivity of IGF-I to mitogenic signals. |
31(0,1,1,1) |