Austin S, Medvedev A, Yan Z H, Adachi H, Hirose T, Jetten A M
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
Cell Growth Differ. 1998 Mar;9(3):267-76.
Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation. RORalpha and RORgamma mRNA were upregulated during adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, whereas RORbeta mRNA could not be detected. The induction of RORalpha and RORgamma mRNA succeeded the induction of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in aP2 and lipoprotein lipase mRNA. Like the expression of PPARgamma and aP2, the induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta. The induction of adipogenesis by prostaglandin D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also accompanied by an induction in RORgamma mRNA. In contrast to parental cells, clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells that ectopically express PPARgamma. RORgamma mediates its effect on transcription through specific response elements. Cotransfection of RORalpha or RORgamma and (RORgamma response element)4-chloramphenicol acetyltransferase into preadipocyte D1 cells induced transactivation of chloramphenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes. The nuclear orphan receptor Rev-ErbAalpha, which did not exhibit transactivation function, was able to inhibit transactivation by RORgamma at two different levels. Our results show that RORgamma is induced during adipocyte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for RORgamma in the regulation of gene expression during this differentiation process.
在此，我们分析了类视黄醇孤儿受体（ROR）核受体亚家族的三个成员在脂肪细胞分化过程中的表达情况。在前脂肪细胞D1和3T3-L1细胞的脂肪细胞分化过程中，RORα和RORγ mRNA表达上调，而未检测到RORβ mRNA。RORα和RORγ mRNA的诱导发生在过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT/增强子结合蛋白α诱导之后，且与aP2和脂蛋白脂肪酶mRNA增加的时间间隔相似。与PPARγ和aP2的表达一样，肿瘤坏死因子α和转化生长因子β可抑制RORγ mRNA的诱导。前列腺素D2和两种噻唑烷二酮在多能干细胞C3H10T1/2中诱导脂肪生成时，也伴随着RORγ mRNA的诱导。与亲代细胞不同，氯贝丁酯在异位表达PPARγ的BALB/c3T3细胞中诱导脂肪生成以及RORα和RORγ mRNA。RORγ通过特定反应元件介导其对转录的影响。将RORα或RORγ与（RORγ反应元件）-氯霉素乙酰转移酶共转染到前脂肪细胞D1中，可诱导氯霉素乙酰转移酶的反式激活增加约100倍，这表明ROR在脂肪细胞基因表达调控中发挥作用。不具有反式激活功能的核孤儿受体Rev-ErbAα能够在两个不同水平抑制RORγ的反式激活。我们的结果表明，RORγ在D1和3T3-L1细胞的脂肪细胞分化过程中被诱导，并作为一种活性转录因子发挥作用，这表明RORγ在该分化过程中的基因表达调控中发挥作用。
