Distinct post-transcriptional regulation of Igfbp1 gene by hypoxia in lowland mouse and Qinghai-Tibet plateau root vole Microtus oeconomus

Our previous study revealed the particular expression patterns of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 1 (IGFBP1) in the Qinghai-Tibet plateau root vole (Microtus oeconomus) under hypoxic challenge. Here we report the molecular mechanisms of Igf gene regulation associated with adaptation to hypoxia. M. oeconomus IGF1 and IGFBP1 were shown to be highly conserved. Hypoxia (8.0% O2, 6 h) did not change the liver-derived Igf1 expression in either M. oeconomus or mouse. Hypoxia significantly upregulated hepatic Igfbp1 gene expression and IGFBP1 levels in the liver and plasma of the mouse, but not in M. oeconomus. A functional U-rich element in the 3′ untranslated region was found in mouse Igfbp1 mRNA, which was associated with Igfbp1 mRNA stabilization and upregulation under hypoxia, and this U-rich element was eliminated in the M. oeconomus Igfbp1, resulting in blunted Igfbp1 mRNA upregulation, which might be understood as a sequence variation modified during molecular evolution under hypoxia.