Role of hypoxia-inducible transcription factors (HIFs) in oxygen-dependent modulation of IGF binding protein–1 biosynthesis in primary rat hepatocytes

Higher levels of IGFBP–1 mRNA are expressed in the less aerobic perivenous zone of the liver. Since gradients in oxygen tension (pO2) may contribute to zonated gene expression, the influence of arterial and venous pO2 on IGFBP–1 biosynthesis was studied in primary cultures of rat hepatocytes. Maximal IGFBP–1 mRNA and protein levels were observed under venous pO2 whereas less than 30% of maximal levels were observed under arterial pO2. In contrast, the expression of IGFBP–4 was greatest under arterial pO2, indicating that this effect of hypoxia on IGFBP–1 gene expression is specific. The response to hypoxia appea…