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Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1

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Abstract

Hypoxia regulates expression of hepatocyte growth factor (HGF) by increasing its transcription and by stabilizing its mRNA. Despite the pivotal role of hypoxia-inducible factor 1 (HIF-1) in transcriptional activation of hypoxia-responsive genes, it is not known whether HIF-1 mediates hypoxia-induced stabilization of HGF mRNA. We constructed adenoviral vectors expressing either the wild-type HIF-1α (Ad2/HIF-1α/FL), a constitutively stable hybrid form of HIF-1α (Ad2/HIF-1α/VP16), or no transgene (Ad2/CMVEV). In rat glioma (C6) cells, human glioma (U251) cells human cardiac, vascular smooth muscle, and endothelial cells, infection with Ad2/HIF-1α/VP16 or Ad2/HIF-1α/FL increased HGF expression at both the mRNA and protein levels. Under normoxic conditions, the half-life of HGF mRNA was 43 min in C6 and U251 cells. Hypoxia and Ad2/HIF-1α/VP16 increased the half-life of HGF mRNA to 3.2 and 2.8 h, respectively, while Ad2/CMVEV had no effect. These studies are the first to demonstrate that overexpression of HIF-1α increases HGF mRNA stability. Our results also suggest that stabilization of HGF mRNA by hypoxia is mediated, at least in part, by HIF-1.

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Acknowledgments

We thank professor Hong Wang at Henry Ford Hospital for critical reading of the paper. This work was supported by a grant 07JWYQ03 from the Training Excellent Youth Teacher Scientific Research Foundation of University of Shanghai, a grant 07XYQ01 from the Excellent Youth Teacher Scientific Research Foundation of Shanghai Jiao Tong University of School of Medicine.

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  1. Department of Neurosurgery, No. 3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 201900, Shanghai, China

    Sheng-Hua Chu, Dong-Fu Feng, Yan-Bin Ma, Zhi-An Zhu, Hong Zhang & Jian-Hua Qiu

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  1. Sheng-Hua Chu
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Chu, SH., Feng, DF., Ma, YB. et al. Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1. Mol Biol Rep 36, 1967–1975 (2009). https://doi.org/10.1007/s11033-008-9406-1

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