A Novel Splicing Variant of Peroxisome Proliferator-Activated Receptor-γ (Pparγ1sv) Cooperatively Regulates Adipocyte Differentiation with Pparγ2.
A Novel Splicing Variant of Peroxisome Proliferator-Activated Receptor-γ (Pparγ1sv) Cooperatively Regulates Adipocyte Differentiation with Pparγ2.
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DOI：
10.1371/journal.pone.0065583
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Katayama S
中科院分区：
文献类型：
--
作者：
Takenaka Y;Inoue I;Nakano T;Shinoda Y;Ikeda M;Awata T;Katayama S
过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPARs）是一类核受体，参与调节细胞分化和发育相关基因的表达。在这里，我们展示了一种新鉴定的编码PPARγ1蛋白的小鼠Pparγ剪接变体（Pparγ 1 sv）的丰富和普遍表达，及其在脂肪形成中的重要性。与Pparγ1和Pparγ2 mRNA相比，新的剪接变体具有独特的5′-UTR序列，表明存在新的转录起始位点和Pparγ表达启动子。Pparγ 1 sv在白色和棕色脂肪组织中高度表达，其水平与Pparγ2相当。Pparγ 1 sv与Pparγ2在3 T3-L1细胞和小鼠原代前脂肪细胞的脂肪分化过程中协同上调。通过特异性siRNA抑制Pparγ 1 sv可完全消除3 T3-L1细胞中诱导的脂肪形成。C/EBPβ和C/EBPδ在3 T3-L1前脂肪细胞中激活Pparγ 1 sv和Pparγ2启动子。提示Pparγ 1 sv和Pparγ2协同调控脂肪细胞分化的早期阶段。
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate expression of a number of genes associated with the cellular differentiation and development. Here, we show the abundant and ubiquitous expression of a newly identified splicing variant of mouse Pparγ (Pparγ1sv) that encodes PPARγ1 protein, and its importance in adipogenesis. The novel splicing variant has a unique 5′-UTR sequence, relative to those of Pparγ1 and Pparγ2 mRNAs, indicating the presence of a novel transcriptional initiation site and promoter for Pparγ expression. Pparγ1sv was highly expressed in the white and brown adipose tissues at levels comparable to Pparγ2. Pparγ1sv was synergistically up-regulated with Pparγ2 during adipocyte differentiation of 3T3-L1 cells and mouse primary cultured preadipocytes. Inhibition of Pparγ1sv by specific siRNAs completely abolished the induced adipogenesis in 3T3-L1 cells. C/EBPβ and C/EBPδ activated both the Pparγ1sv and Pparγ2 promoters in 3T3-L1 preadipocytes. These findings suggest that Pparγ1sv and Pparγ2 synergistically regulate the early stage of the adipocyte differentiation.
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DOI：
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影响因子：
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