School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China.
School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China.
J Endocrinol. 2021 Apr 27;249(2):149-161. doi: 10.1530/JOE-20-0561.
Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4-induced liver fibrosis. However, the mechanism of YAP during hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4 months of high-fat diet (HFD) stimulation, and we found that the YAP signaling pathway was activated. Here, we aim to reveal whether specific knockout of Yap gene in the liver can improve liver fibrosis induced by insulin resistance (IR) stimulated by HFD, and further explain its specific mechanism. We found that liver-specific Yap gene knockout improved IR-induced liver fibrosis and liver dysfunction, and this mechanism is related to the inhibition of the insulin signal pathway at the FoxO1 level. These findings provide a new insight, and Yap is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.
Yes 相关蛋白 (YAP) 作为转录因子的共激活因子，是 Hippo 信号通路中的下游蛋白，在细胞增殖、凋亡、侵袭和迁移中具有重要功能。YAP 在 CCl4 诱导的肝纤维化发展中也起着关键作用。然而，YAP 在肝纤维化进展和逆转过程中的机制尚不清楚。经过 4 个月高脂肪饮食 (HFD) 刺激后，我们发现 YAP 信号通路被激活。在这里，我们旨在揭示肝脏中 Yap 基因的特异性敲除是否可以改善由 HFD 刺激的胰岛素抵抗 (IR) 引起的肝纤维化，并进一步解释其具体机制。我们发现，肝脏特异性 yap 基因敲除可改善 IR 诱导的肝纤维化和肝功能障碍，其机制与 FoxO1 水平的胰岛素信号通路抑制有关。这些发现提供了一个新的视角，YAP 有望成为逆转 IR 诱导的早期肝纤维化的新靶点。
