The activation of peroxisome proliferator-activated receptor γ is regulated by Kruppel-like transcription factors 6 & 9 under steatotic conditions
The activation of peroxisome proliferator-activated receptor γ is regulated by Kruppel-like transcription factors 6 & 9 under steatotic conditions
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DOI：
10.1016/j.bbrc.2015.01.145
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发表时间：
2015-03-20
影响因子：
3.1
通讯作者：
Perez-Monter, Carlos
中科院分区：
文献类型：
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作者：
Escalona-Nandez, Ivonne;Guerrero-Escalera, Dafne;Perez-Monter, Carlos
肝脂肪变性的特征在于肝细胞中的脂滴沉积，其可导致炎性和纤维化表型。过氧化物酶体增殖物激活受体（PPARs）通过调节肝组织脂质代谢，在维持能量平衡中发挥重要作用。在脂肪组织中，PPAR γ通过促进脂质相关基因的表达来调节脂肪细胞的分化。在脂肪变性条件下，肝脏内的PPAR γ上调;然而，哪些转录因子参与其表达尚不完全清楚。Kruppel样转录因子（KLF）调节多种细胞机制，例如细胞增殖和分化。KLF是脂肪形成的关键成分，通过调节PPAR γ和其他蛋白质如C末端增强子结合蛋白（C/EBP）的表达。在这里，我们证明了Klf 6，Klf 9和Ppar γ的转录水平在体外脂肪变性损伤时增加。染色质免疫沉淀（ChIp）实验表明，在这些条件下，klf 6和klf 9被主动募集到Ppar γ启动子区域。因此，功能丧失实验减少了细胞质甘油三酯蓄积。在这里，我们证明了KLF 6和KLF 9蛋白直接调节脂肪变性条件下的PPAR γ表达。(C)2015 Elsevier Inc. All rights reserved.
Liver steatosis is characterised by lipid droplet deposition in hepatocytes that can leads to an inflammatory and fibrotic phenotype. Peroxisome proliferator-activated receptors (PPARs) play key roles in energetic homeostasis by regulating lipid metabolism in hepatic tissue. In adipose tissue PPAR gamma regulates the adipocyte differentiation by promoting the expression of lipid-associated genes. Within the liver PPAR gamma is up-regulated under steatotic conditions; however, which transcription factors participate in its expression is not completely understood. Kruppel-like transcription factors (KLFs) regulate various cellular mechanisms, such as cell proliferation and differentiation. KLFs are key components of adipogenesis by regulating the expression of PPAR gamma and other proteins such as the C-terminal enhancer binding protein (C/EBP). Here, we demonstrate that the transcript levels of Klf6, Klf9 and Ppar gamma are increased in response to a steatotic insult in vitro. Chromatin immunoprecipitation (ChIp) experiments showed that klf6 and klf9 are actively recruited to the Ppar gamma promoter region under these conditions. Accordingly, the loss-of-function experiments reduced cytoplasmic triglyceride accumulation. Here, we demonstrated that KLF6 and KLF9 proteins directly regulate PPAR gamma expression under steatotic conditions. (C) 2015 Elsevier Inc. All rights reserved.