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Effect of hypoxia on the gene profile of human bone marrow--derived mesenchymal stem cells

Wu Enhui, Li Haisheng, Zhao Tong, Fan Jundie, Ma Xin, Xiong Lei, Li Wuju, Zhu Lingling, Fan Ming

Institute of Basic Medicine,Academy of Military Medical Science.Beijing 100850

Abstract

Our previous study demonstrates that hypoxia promotes human bone marrow-derived mesenchymal stem cell (hMSC) proliferation. The aim of the present study was to investigate the gene profile involved in this process by using cDNA microarray. Cultured hMSCs were treated with hypoxia (3% O_(2)) for 4 h, 12 h, 24 h, 36 h, 48 h and 72 h, respectively. Then these cells were collected to prepare total RNA. Hypoxia-induced gene expression profile was examined and analyzed by GenePix Pro 4.0 software. Some of cDNA microarray results were confirmed by RT-PCR. Microarray analysis indentified that 282 genes expressed differentially, of which most are involved in metabolism. The number of differentially expressed genes at different hypoxia time points was different，and most genes were regulated after 24-hour hypoxia. Among the 282 differentially expressed genes, 4 HIF-1 targeted genes and 10 genes that changed on 3 continuous time points were found. The results obstained indicated that 4 HIF-1 targeted genes, i.e., transforming growth factor #beta#3 (TGF#beta#3), phosphoglycerate kinase 1 (PGK1), insulin-like growth factor binding protein 3 (IGFBP3) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), displayed up-regulated pattern at 36 h under hypoxia. BNIP3 displayed a dynamically up-regulated pattern at 12, 36 and 72 h under hypoxia. However, TGF#beta#3 and PGK1 were down-regulated at 72 h. In addition, the gene expressions of adenylate kinase 3-like 1 (HAC), neurofilament light polypeptide 68 kDa (NEFL), N-myc downstream regultated gene 1 (NDRG1), discoidin domain receptor family member 1 (DDR1), tribbles homolog 3 (TRIB3), nucleoprotein (AHNAK) and eukaryotic elongation factor selenocyteine-tRNA-specific (EESTS) were up-regulated. Moreover, the gene expressions of EESTS, NEFL were up-regulated at 5 different time points under hypoxia. Furthermore, it was found that the gene expressions of histone cluster 1 (HIS1) and transferring receptor (TFRC) were down-regulated. Our results suggest that the proliferation of hMSCs induced by hypoxia is a complex process in which a number of genes may be involved.

Key words: Hypoxia;human bone marrow-derived mesenchymal stem cells;cDNA microarray;differentially expressed genes

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Citing This Article：

Wu Enhui, Li Haisheng, Zhao Tong, Fan Jundie, Ma Xin, Xiong Lei, Li Wuju, Zhu Lingling, Fan Ming. Effect of hypoxia on the gene profile of human bone marrow--derived mesenchymal stem cells. Acta Physiol Sin 2007; 59 (2): 227-232 (in Chinese with English abstract).