Hypoxia-Inducible Factor-3α Functions as an Accelerator of 3T3-L1 Adipose Differentiation
Hypoxia-Inducible Factor-3α Functions as an Accelerator of 3T3-L1 Adipose Differentiation
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DOI：
10.1248/bpb.32.1166
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Hara, Shuntaro
中科院分区：
文献类型：
--
作者：
Hatanaka, Misaki;Shimba, Shigeki;Hara, Shuntaro
缺氧诱导因子（HIF）是由HIF-α和HIF-β组成的异源二聚体，迄今为止，已经鉴定出三种HIF-α亚基，HIF-1 α、HIF-2 α和HIF-3 α。在这些HIF-α亚基中，HIF-1 α抑制过氧化物酶体增殖物激活剂γ 2基因表达，然后抑制脂肪形成，而HTF-2 α在脂肪分化过程中被诱导，并作为脂肪形成的正调节剂发挥作用。我们在此发现，与HIF-2 α一样，HIF-3 α在3 T3-L1脂肪分化过程中被诱导。报告基因分析显示，HIF-2a增强了小鼠HIF-3 α基因5 '侧翼区（核苷酸-2710至+56）的启动子活性，而HIT-1 α对启动子活性没有实质性影响。这些结果表明，在脂肪形成过程中诱导的HIF-2 α可能调节HIF-3 α基因的表达。此外，5 '-缺失分析显示小鼠HIF-3 α启动子中-251和-228之间的序列是响应HIF-2 α所必需的。我们进一步研究了HIF-3 α在3 T3-L1细胞中的异位表达对脂肪分化的影响，发现HIF-3 α在分化早期的异位表达诱导了多种脂肪细胞相关基因的表达，并增强了脂肪细胞的成脂潜力。HIF-2 α诱导的HIF-3 α可能作为脂肪生成的加速剂发挥作用。
Hypoxia-inducible factor (HIF) is a heterodimer composed of HIF-alpha and -beta, and to date, three HIF-alpha subunits, HIF-1 alpha, -2 alpha, and -3 alpha, have been identified. Among these HIF-alpha subunits, HIF-1 alpha represses peroxisome proliferator activator gamma 2 gene expression and then inhibits adipogenesis, and HTF-2 alpha is induced during adipose differentiation and functions as a positive regulator of adipogenesis. We here found that like HIF-2 alpha HIF-3 alpha was induced during 3T3-L1 adipose differentiation. Reporter gene analysis revealed that HIF-2a enhanced the promoter activity, of the 5'-flanking region of the mouse HIF-3 alpha gene (nucleotides -2710 to +56), while HIT-1 alpha had no substantial effects on the promoter activity. These results suggested that HIF-2 alpha which was induced during adipogenesis, might regulate the HIF-3 alpha gene expression. Furthermore, the 5'-deletion analysis revealed that the sequence between -251 and -228 in mouse HIF-3 alpha promoter was essential in response to HIF-2 alpha. We further examined the effect of ectopic expression of HIF-3 alpha in 3T3-L1 cells on adipose differentiation and found that ectopic expression of HIF-3 alpha at the early stage of differentiation induced the expression of several kinds of adipocytes-related genes and enhanced adipogenic potential. HIF-3 alpha, which is induced by HIF-2 alpha, might function as an accelerator of adipogenesis.