Jin Wanzhu, Takagi Tsuyoshi, Kanesashi Shin-nosuke, Kurahashi Toshihiro, Nomura Teruaki, Harada Jun, Ishii Shunsuke
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Dev Cell. 2006 Apr;10(4):461-71. doi: 10.1016/j.devcel.2006.02.016.
Adipocyte differentiation is an important component of obesity, but how hormonal cues mediate adipocyte differentiation remains elusive. BMP stimulates in vitro adipocyte differentiation, but the role of BMP in adipogenesis in vivo is unknown. Drosophila Schnurri (Shn) is required for the signaling of Decapentaplegic, a Drosophila BMP homolog, via interaction with the Mad/Medea transcription factors. Vertebrates have three Shn orthologs, Shn-1, -2, and -3. Here, we report that Shn-2(-/-) mice have reduced white adipose tissue and that Shn-2(-/-) mouse embryonic fibroblasts cannot efficiently differentiate into adipocytes in vitro. Shn-2 enters the nucleus upon BMP-2 stimulation and, in cooperation with Smad1/4 and C/EBPalpha, induces the expression of PPARgamma2, a key transcription factor for adipocyte differentiation. Shn-2 directly interacts with both Smad1/4 and C/EBPalpha on the PPARgamma2 promoter. These results indicate that Shn-2-mediated BMP signaling has a critical role in adipogenesis.
脂肪细胞分化是肥胖的一个重要组成部分，但激素信号如何介导脂肪细胞分化仍不清楚。骨形态发生蛋白（BMP）可刺激体外脂肪细胞分化，但BMP在体内脂肪生成中的作用尚不清楚。果蝇的Schnurri（Shn）蛋白通过与Mad/Medea转录因子相互作用，参与果蝇BMP同源物Decapentaplegic的信号传导。脊椎动物有三个Shn同源物，即Shn-1、-2和-3。在此，我们报道Shn-2基因敲除小鼠的白色脂肪组织减少，并且Shn-2基因敲除小鼠胚胎成纤维细胞在体外不能有效地分化为脂肪细胞。BMP-2刺激后，Shn-2进入细胞核，并与Smad1/4和C/EBPα协同作用，诱导脂肪细胞分化关键转录因子PPARγ2的表达。Shn-2直接与PPARγ2启动子上的Smad1/4和C/EBPα相互作用。这些结果表明，Shn-2介导的BMP信号在脂肪生成中起关键作用。
