Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2.
Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2.
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Hilnc 的缺失通过结合 IGF2BP2 预防饮食诱导的肝脂肪变性
DOI：
10.1038/s42255-021-00488-3
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发表时间：
2021-11
影响因子：
20.8
通讯作者：
Zhao, Yun
中科院分区：
文献类型：
--
作者：
Jiang, Yiao;Peng, Jiayin;Song, Jiawen;He, Juan;Jiang, Man;Wang, Jia;Ma, Liya;Wang, Yuang;Lin, Moubin;Wu, Hailong;Zhang, Zhao;Gao, Dong;Zhao, Yun
Hedgehog(HH)信号通路在调节肝脏脂质代谢和相关疾病中起着关键作用。然而，人们对其潜在的机制知之甚少。在这里，我们证明了HH信号通路诱导了一个以前未定义的长非编码RNA(Hilnc，Hedgehog Signing-Induced Long Non-Coding RNA)，它控制着肝脏的脂肪代谢。Hilnc启动子区域Gli结合位点的突变(HilncBM/BM)在体外和体内都降低了Hilnc的表达。HilncBM/BMandHilnc基因敲除小鼠通过减弱过氧化体增殖物激活受体信号通路来抵抗饮食诱导的肥胖和肝脏脂肪变性，因为Hilnc直接与IGF2BP2相互作用，增强PparγmR NA的稳定性。此外，我们还鉴定了一种潜在的人类同源物h-Hilnc，它在调节细胞脂质代谢方面具有类似的功能。这些发现揭示了HH-Hilnc-IGF2BP2信号轴在脂质代谢中的关键作用，并为饮食诱导的肝脏脂肪变性的治疗提供了潜在的治疗靶点。
The Hedgehog (Hh) signalling pathway plays a critical role in regulating liver lipid metabolism and related diseases. However, the underlying mechanisms are poorly understood. Here, we show that the Hh signalling pathway induces a previously undefined long non-coding RNA (Hilnc, Hedgehog signalling-induced long non-coding RNA), which controls hepatic lipid metabolism. Mutation of the Gli-binding sites in theHilncpromoter region (HilncBM/BM) decreases the expression of Hilnc in vitro and in vivo.HilncBM/BMandHilnc-knockout mice are resistant to diet-induced obesity and hepatic steatosis through attenuation of the peroxisome proliferator-activated receptor signalling pathway, as Hilnc directly interacts with IGF2BP2 to enhancePparγmRNA stability. Furthermore, we identify a potential functional human homologue of Hilnc, h-Hilnc, which has a similar function in regulating cellular lipid metabolism. These findings uncover a critical role of the Hh-Hilnc–IGF2BP2 signalling axis in lipid metabolism and suggest a potential therapeutic target for the treatment of diet-induced hepatic steatosis.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
DOI：
10.1016/j.biocel.2010.10.015
发表时间：
2011-02
影响因子：
4
作者：
Choi, Steve S.;Omenetti, Alessia;Syn, Wing-Kin;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae
影响因子：
8
作者：
Chan, L. H.;Wang, W.;Mak, K. K.
通讯作者：
Mak, K. K.
影响因子：
64.5
作者：
Hallikas, O;Palin, K;Taipale, J
通讯作者：
Taipale, J
DOI：
10.1073/pnas.1004602107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Lee, Eunice Y.;Ji, Hongkai;Scott, Matthew P.
通讯作者：
Scott, Matthew P.