关键词： CDK, cyclin-dependent kinase EGF, epidermal growth factor EGFR, EGF receptor ERK, extracellular signal-regulated kinase FAH, fumarylacetoacetate hydrolase GH, growth hormone Ghr-/-, growth hormone receptor gene knockout HGF, hepatocyte growth factor HNF, hepatocyte nuclear factor HPC, hepatic progenitor cell IGF, insulinlike growth factor IL, interleukin IR, insulin receptor InsP3, inositol 1,4,5-trisphosphate JNK, JUN N-terminal kinase LDLT, living donor liver transplant LRP, low-density lipoprotein-related protein MAPK, mitogen-activated protein kinase NF-κβ, nuclear factor κβ NOS, nitric oxide synthase NTBC, 2-nitro-4-trifluoro-methyl-benzoyl-1,3-cyclohexanedione PCNA, proliferating cell nuclear antigen PCR, polymerase chain reaction PH, partial hepatectomy PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase PKB, protein kinase B PTU, 6-n-propyl-2-thiouracil ROS, reactive oxygen species STAT, signal transducer and activator of transcription T3, triiodothyronine TGF, transforming growth factor TNF, tumor necrosis factor TR, thyroid receptor hESC, human embryonic stem cell hiPSC, human induced pluripotent stem cells mRNA, messenger RNA mTOR, mammalian target of rapamycin

来  源：   DOI：10.1016/j.mayocpiqo.2020.02.001   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient (FAH -/-) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κβ, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019.
摘要：
对肝再生的分子基础的理解将为慢性肝衰竭的新疗法的开发开辟新的视野。这种疗法将解决与肝移植相关的缺点，包括供体器官的短缺,漫长的等候时间，高昂的医疗费用,和终生使用免疫抑制剂。已经在动物模型中研究了部分肝切除术后的再生，特别是富马酸乙酰乙酸水解酶缺陷（FAH-/-）小鼠和猪。再生的过程是独特的，复杂，协调良好，它取决于几种信号通路之间的相互作用(例如，核因子κβ,缺口,河马),细胞因子(例如，肿瘤坏死因子α,白细胞介素6)，和生长因子(例如，肝细胞生长因子，表皮生长因子，血管内皮生长因子)，和其他组件。此外，内分泌激素（例如，去甲肾上腺素,生长激素,胰岛素，甲状腺激素）也可以影响上述途径和因素。我们认为，这些内分泌激素是重要的肝有丝分裂原，通过直接和间接触发所涉及的信号通路的活性，强烈诱导和加速肝细胞增殖（再生），细胞因子,生长因子，和转录因子。随后诱导细胞周期蛋白和相关的细胞周期蛋白依赖性激酶复合物允许肝细胞进入细胞周期。在这篇评论文章中，我们全面总结了目前有关这些激素在肝再生中的作用和机制的知识。从开始到2019年6月1日，通过搜索MEDLINE和EMBASE数据库来确定用于本评论的文章。
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