Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis.
Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis.
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DOI：
10.1002/hep.29654
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Liu C;Yang Z;Wu J;Zhang L;Lee S;Shin DJ;Tran M;Wang L
H19是一种印迹的长非编码RNA，在胚胎肝脏中大量表达，出生后被抑制。在这里，我们表明，H19作为一个脂质传感器协同RNA结合蛋白PTBP 1调节肝脏代谢稳态。H19 RNA与PTBP 1相互作用以促进其与SREBP 1c mRNA和蛋白的结合，从而增加稳定性和核转录活性。H19和PTBP 1在肝细胞和饮食诱导的脂肪肝中被脂肪酸上调，这进一步增加了脂质积累。H19的异位表达诱导脂肪变性，并通过促进SREBP 1c蛋白裂解和核转位将肝脏推向响应禁食的“假进食”状态。H19的缺失或PTBP 1的敲低消除了高脂肪和高蔗糖（HFHS）饮食诱导的脂肪变性。我们的研究揭示了H19/PTBP 1/SREBP 1前馈放大信号通路加剧脂肪肝的发展。
H19 is an imprinted long non-coding RNA abundantly expressed in embryonic liver and repressed after birth. Here we show that H19 serves as a lipid sensor by synergizing with RNA-binding protein PTBP1 to modulate hepatic metabolic homeostasis. H19RNA interacts with PTBP1 to facilitate its association with SREBP1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are upregulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation. Ectopic expression of H19 induces steatosis and pushes the liver into a “pseudo fed” state in response to fasting by promoting SREBP1c protein cleavage and nuclear translocation. Deletion of H19 or knockdown of PTBP1 abolishes high-fat and high-sucrose (HFHS) diet-induced steatosis. Our study unveils a H19/PTBP1/SREBP1 feedforward amplifying signaling pathway to exacerbate the development of fatty liver.
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DOI：
10.1002/hep.29209
发表时间：
2017-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Song Y;Liu C;Liu X;Trottier J;Beaudoin M;Zhang L;Pope C;Peng G;Barbier O;Zhong X;Li L;Wang L
通讯作者：
Wang L
影响因子：
29.4
作者：
Tsuchiya H;da Costa KA;Lee S;Renga B;Jaeschke H;Yang Z;Orena SJ;Goedken MJ;Zhang Y;Kong B;Lebofsky M;Rudraiah S;Smalling R;Guo G;Fiorucci S;Zeisel SH;Wang L
通讯作者：
Wang L
影响因子：
5.1
作者：
Yang Z;Ross RA;Zhao S;Tu W;Liangpunsakul S;Wang L
通讯作者：
Wang L
影响因子：
64.5
作者：
Gomez JA;Wapinski OL;Yang YW;Bureau JF;Gopinath S;Monack DM;Chang HY;Brahic M;Kirkegaard K
通讯作者：
Kirkegaard K
影响因子：
15.9
作者：
Watanabe, M;Houten, SM;Auwerx, J
通讯作者：
Auwerx, J