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Review
. 2021 Nov;9(22):1705.
doi: 10.21037/atm-21-5234.

A narrative review of liver regeneration-from models to molecular basis

Affiliations
Review

A narrative review of liver regeneration-from models to molecular basis

Wei Huang et al. Ann Transl Med. 2021 Nov.

Abstract

Objective: To elucidate the characteristics of different liver regeneration animal models, understand the activation signals and mechanisms related to liver regeneration, and obtain a more comprehensive conception of the entire liver regeneration process.

Background: Liver regeneration is one of the most enigmatic and fascinating phenomena of the human organism. Despite suffering significant injuries, the liver still can continue to perform its complex functions through the regeneration system. Although advanced topics on liver regeneration have been proposed; unfortunately, complete regeneration of the liver has not been achieved until now. Therefore, increasing understanding of the liver regenerative process can help improve our treatment of liver failure. It will provide a new sight for the treatment of patients with liver injury in the clinic.

Methods: Literatures on liver regeneration animal models and involved basic research on molecular mechanisms were retrieved to analyze the characteristics of different models and those related to molecular basis.

Conclusions: The process of liver regeneration is complex and intricate, consisting of various and interactive pathways. There is sufficient evidence to demonstrate that liver regeneration is similar between humans and rodents. At the same time, many of the same cytokines, growth factors, and signaling pathways are relevant. There are many gaps in our current knowledge. Understanding of this knowledge will provide more supportive clinical treatment strategies, including small-scale liver transplantation and high-quality regenerative process after surgical resection, and offer possible targets to treat the dysregulation of regeneration that occurs in chronic hepatic diseases and tumors. Current research work, such as the use of animal models as in vivo vectors for high-quality human hepatocytes, represents a unique and significant cutting edge in the field of liver regeneration.

Keywords: Liver regeneration; animal model; cytokines; signaling pathways.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-5234). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Common animal models of liver regeneration. PHx, partial hepatectomy; CCL4, carbon tetrachloride; D-gal, D-galactosamine; APAP, acetaminophen; TAA, thioacetamide.
Figure 2
Figure 2
Cytokines, growth factors, and signaling pathways contributing to liver regeneration after PHx. NF-κB, nuclear factor kappa B; IL-6, interleukin-6; TNF-α, tumor necrosis factor α; p130, glycoprotein 130 kDa; STAT3, signal transducer and activator of transcription 3; JNK, c-Jun N-terminal kinase; LPR5/6, low-density lipoprotein receptor-related protein 5/6; Gsk3β, glycogen synthase kinase 3 beta; Axin, axis inhibition protein; Dvl, dishevelled; APC, adenomatous polyposis coli; CK1α, casein kinase 1; TCF/LEF, T cell factor/lymphoid enhancer factor; uPA, urokinase-type plasminogen activator; HGF, hepatocyte growth factor; pro-HGF, inactive precursor of HGF; c-Met, hepatocyte growth factor receptor; EGF, endothelial growth factor; EGFR, EGR receptor; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; TSC1/2, tuberous sclerosis complex1/2; Rheb, small guanosine triphosphatase; mTOR, mammalian target of rapamycin; p70S6K1, p70 S6 kinase 1; 4E-BP, 4E-binding protein; Ras/Raf/MEK/Erk (also known as MAPK), mitogen-activated protein kinases.

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