Deng Jiangming, Teng Jianhui, Xiao Ting, Wen Jie, Meng Wen
National Clinical Research Center for Metabolic Diseases and the Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
The Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Heliyon. 2024 May 15;10(10):e31312. doi: 10.1016/j.heliyon.2024.e31312. eCollection 2024 May 30.
Numerous researches have reported on the regulatory network of liver regeneration induced by partial hepatectomy (PH). However, information on key molecules and/or signaling pathways regulating the termination stage of liver regeneration remains limited. In this study, we identify hepatic mitotic arrest deficient 1 (MAD1) as a crucial regulator of transforming growth factor β (TGF-β) in the hepatocyte to repress liver regeneration. MAD1 has a low expression level at the rapid proliferation phase but significantly increases at the termination phase of liver regeneration. We show that MAD1 deficiency accelerates hepatocyte proliferation and enhances mitochondrial biogenesis and respiratory. Mechanistically, MAD1 deficiency in hepatocytes enhances mitochondrial function and promotes hepatocyte proliferation by suppressing TGF-β signaling. Our study reveals MAD1 as a novel suppressor of hepatocyte proliferation, which may provide a new therapeutic target for the recovery of liver function after liver transplant and partial hepatectomy.
众多研究已报道了部分肝切除术（PH）诱导的肝再生调控网络。然而，关于调节肝再生终止阶段的关键分子和/或信号通路的信息仍然有限。在本研究中，我们确定肝有丝分裂停滞缺陷蛋白1（MAD1）是肝细胞中转化生长因子β（TGF-β）的关键调节因子，可抑制肝再生。MAD1在肝再生的快速增殖阶段表达水平较低，但在终止阶段显著增加。我们表明，MAD1缺陷会加速肝细胞增殖，并增强线粒体生物发生和呼吸作用。从机制上讲，肝细胞中的MAD1缺陷通过抑制TGF-β信号传导增强线粒体功能并促进肝细胞增殖。我们的研究揭示MAD1是肝细胞增殖的新型抑制因子，这可能为肝移植和部分肝切除术后肝功能恢复提供新的治疗靶点。
