1. Hormonal Contribution to Liver Regeneration
- Author
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Wei Zhou, Anan Abu Rmilah, and Scott L. Nyberg
- Subjects
NTBC, 2-nitro-4-trifluoro-methyl-benzoyl-1,3-cyclohexanedione ,Review ,hESC, human embryonic stem cell ,030204 cardiovascular system & hematology ,HPC, hepatic progenitor cell ,PCR, polymerase chain reaction ,0302 clinical medicine ,ERK, extracellular signal-regulated kinase ,Epidermal growth factor ,Medicine ,030212 general & internal medicine ,NOS, nitric oxide synthase ,TGF, transforming growth factor ,CDK, cyclin-dependent kinase ,TNF, tumor necrosis factor ,lcsh:R5-920 ,FAH, fumarylacetoacetate hydrolase ,mRNA, messenger RNA ,Liver regeneration ,Ghr-/-, growth hormone receptor gene knockout ,STAT, signal transducer and activator of transcription ,JNK, JUN N-terminal kinase ,Hepatocyte nuclear factors ,IR, insulin receptor ,EGFR, EGF receptor ,Hepatocyte growth factor ,HNF, hepatocyte nuclear factor ,lcsh:Medicine (General) ,medicine.drug ,PKB, protein kinase B ,PH, partial hepatectomy ,PCNA, proliferating cell nuclear antigen ,mTOR, mammalian target of rapamycin ,03 medical and health sciences ,ROS, reactive oxygen species ,hiPSC, human induced pluripotent stem cells ,PI3K/AKT/mTOR pathway ,EGF, epidermal growth factor ,T3, triiodothyronine ,business.industry ,Regeneration (biology) ,NF-κβ, nuclear factor κβ ,IGF, insulinlike growth factor ,PTU, 6-n-propyl-2-thiouracil ,GH, growth hormone ,IL, interleukin ,InsP3, inositol 1,4,5-trisphosphate ,PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase ,Cancer research ,TR, thyroid receptor ,HGF, hepatocyte growth factor ,LRP, low-density lipoprotein-related protein ,business ,LDLT, living donor liver transplant ,MAPK, mitogen-activated protein kinase ,Transforming growth factor ,Hormone - 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.
- Published
- 2020