Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis
Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis
复制标题
DOI：
10.1074/jbc.m410515200
复制
发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Mori, T;Sakaue, H;Kasuga, M
Kruppel 样锌指转录因子 (KLF) 在哺乳动物细胞分化和发育过程中发挥着多种作用。我们现在通过微阵列分析表明，在3T3-L1前脂肪细胞分化为脂肪细胞的过程中，KLF15基因的表达显着上调。通过显性失活突变体的表达或通过RNA干扰抑制KLF15的功能，都可以减少过氧化物酶体增殖物激活受体γ（PPARγ）的表达，并阻断暴露于脂肪细胞分化诱导剂的3T3-L1前脂肪细胞中的脂肪生成。然而，KLF15 的显性失活突变体并不影响 3T3-L1 前脂肪细胞中分化诱导剂诱导的 CCAAT/增强子结合蛋白 β (C/EBP β) 的表达。此外，在脂肪细胞分化诱导剂存在的情况下，NIH 3T3 或 C2C12 细胞中 KLF15 的异位表达会触发脂质积累和 PPAR γ 的表达。在脂肪细胞分化诱导剂存在的情况下，NIH 3T3 细胞中 C/EBP β、C/EBP δ 或 C/EBP α 的异位表达也会引发 KLF15 的表达。此外，KLF15 和 C/EBP α 协同作用，增加 3T3-L1 脂肪细胞中 PPAR γ 2 基因启动子的活性。因此，我们的观察结果表明，KLF15 通过调节 PPAR γ 表达，在 3T3-L1 细胞的脂肪生成中发挥重要作用。
Kruppel-like zinc finger transcription factors (KLFs) play diverse roles during cell differentiation and development in mammals. We have now shown by microarray analysis that expression of the KLF15 gene is markedly up-regulated during the differentiation of 3T3-L1 preadipocytes into adipocytes. Inhibition of the function of KLF15, either by expression of a dominant negative mutant or by RNA interference, both reduced the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and blocked adipogenesis in 3T3-L1 preadipocytes exposed to inducers of adipocyte differentiation. However, the dominant negative mutant of KLF15 did not affect the expression of CCAAT/enhancer-binding protein beta (C/EBP beta) elicited by inducers of differentiation in 3T3-L1 preadipocytes. In addition, ectopic expression of KLF15 in NIH 3T3 or C2C12 cells triggered both lipid accumulation and the expression of PPAR gamma in the presence of inducers of adipocyte differentiation. Ectopic expression of C/EBP beta, C/EBP delta, or C/EBP alpha in NIH 3T3 cells also elicited the expression of KLF15 in the presence of inducers of adipocyte differentiation. Moreover, KLF15 and C/EBP alpha acted synergistically to increase the activity of the PPAR gamma 2 gene promoter in 3T3-L1 adipocytes. Our observations thus demonstrate that KLF15 plays an essential role in adipogenesis in 3T3-L1 cells through its regulation of PPAR gamma expression.