Starvation‐induced transcription factor CREBH negatively governs body growth by controlling GH signaling
Starvation‐induced transcription factor CREBH negatively governs body growth by controlling GH signaling
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饥饿诱导的转录因子 CREBH 通过控制 GH 信号传导负调控身体生长
DOI：
10.1096/fj.202002784rr
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Shi
中科院分区：
文献类型：
--
作者：
Nakagawa Yoshimi;Kumagai Kae;Han Song‐iee;Mizunoe Yuhei;Araki Masaya;Mizuno Seiya;Ohno Hiroshi;Matsuo Kazuya;Yamada Yasunari;Kim Jun‐dal;Miyamoto Takafumi;Sekiya Motohiro;Konishi Morichika;Itoh Nobuyuki;Matsuzaka Takashi;Takahashi Satoru;Sone Hirohito;Shi
cAMP反应元件结合蛋白H（CREBH）是一种在禁食期间被激活的肝脏转录因子。我们产生了CREBH敲入flox小鼠，然后产生了活性形式的肝脏特异性CREBH转基因（CREBH L-Tg）小鼠。CREBH L-Tg小鼠在出生后阶段表现出生长延迟。CREBH L-Tg小鼠的血浆生长激素（GH）水平显著升高，但血浆胰岛素样生长因子1（IGF 1）水平显著降低，表明GH抵抗。此外，CREBH过表达显著增加肝脏mRNA和血浆FGF 21水平，这被认为是生长延迟的原因之一。然而，CREBH L-Tg小鼠中FGF 21的额外消融根本不能纠正GH抗性。CREBH L-Tg小鼠持续GH受体（GHR）减少和肝脏中IGF结合蛋白1（IGFBP 1）增加，与FGF 21无关。由于GHR是GH信号传导的第一步，因此GHR的降低导致GH信号传导受损。这些数据表明，CREBH负调控生长在出生后的生长阶段，通过各种途径作为一个丰富的能量反应，通过拮抗GH信号。
cAMP responsive element‐binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock‐in flox mice, and then generated liver‐specific CREBH transgenic (CREBH L‐Tg) mice in an active form. CREBH L‐Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L‐Tg mice, but plasma insulin‐like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L‐Tg mice could not correct GH resistance at all. CREBH L‐Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.
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DOI：
10.1152/ajpendo.00389.2003
发表时间：
2004-03
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
J. Woelfle;P. Rotwein
通讯作者：
J. Woelfle;P. Rotwein
影响因子：
29
作者：
Dong XC;Copps KD;Guo S;Li Y;Kollipara R;DePinho RA;White MF
通讯作者：
White MF
影响因子：
4.8
作者：
H. W. Davey;Tao Xie;Tao Xie;Michael J Mclachlan;R. Wilkins;D. Waxman;D. Grattan
通讯作者：
H. W. Davey;Tao Xie;Tao Xie;Michael J Mclachlan;R. Wilkins;D. Waxman;D. Grattan
影响因子：
--
作者：
Ono, Mitsuru;Chia, Dennis J.;Rotwein, Peter
通讯作者：
Rotwein, Peter
DOI：
10.1073/pnas.94.14.7239
发表时间：
1997-07-08
影响因子：
11.1
作者：
Udy, GB;Towers, RP;Davey, HW
通讯作者：
Davey, HW