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Northern blot analysis revealed a marked increase in IGFBP-1 mRNA levels, with a maximum between 3 and 9 h after CCl4 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\u201312 h after CCl4 application, extending to the midzonal region of the acinus within 24\u201348 h. Consequently, a prominent immunostaining for IGFBP-1 was observed in perivenous areas, with a maximum 24\u201348 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.<\/jats:p>","DOI":"10.1210\/en.2003-1541","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T00:23:51Z","timestamp":1081815831000},"page":"3463-3472","source":"Crossref","is-referenced-by-count":25,"title":["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"],"prefix":"10.1210","volume":"145","author":[{"given":"Jens-Gerd","family":"Scharf","sequence":"first","affiliation":[{"name":"Department of Medicine (J.-G.S., R.N., C.E.), University of Go\u0308ttingen, D-37099 Go\u0308ttingen, 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