Hallmarks of postoperative liver regeneration: An updated insight on the regulatory mechanisms

Abstract

Performance and advances in liver surgery makes remarkable progress of the understanding of liver regeneration. Liver regeneration after liver resection has been widely researched, and the underlying mechanism mostly concerns proliferation of hepatocytes and the influence by inflammation through activation of Kupffer cells and the other parenchymal cells, the second regenerative pathway by hepatic progenitor cells (HPCs), inducing angiogenesis, remodeling of a extracellular matrix (ECM), and termination mechanisms. New clinical surgeries and the updated multiomics analysis are exploiting the remarkable progress, especially in immune regulation and metabolic process of two emerging hallmarks. This review briefly represents a systemic outline of eight hallmarks, including hepatocyte proliferation, contribution of hepatic progenitor cells, inducing angiogenesis, reprogramming of the extracellular matrix, apoptosis and termination of proliferation, inflammation, immune and metabolic regulation, which are set as organizing characteristics of postoperative liver regeneration and future directions of refining treatment targets.

Lactiplantibacillus plantarum AR113 Exhibit Accelerated Liver Regeneration by Regulating Gut Microbiota and Plasma Glycerophospholipid

“…In the liver, IL-6 is secreted by Kupffer cells, and this secretion is stimulated by TNF-α (Jin et al, 2021). HGF is a 97-kd protein that was originally isolated from the peripheral blood of animals after PHx, which is known to be essential to initiate the process of liver regeneration (Gao and Peng, 2021); it could rapidly be elevated by 10-to 20-fold at the early stage of liver injury (Shi and Line, 2020). Present study showed that L. plantarum AR113 given two weeks before PHx significantly increased the expression of TNF-α after PHx.…”

Liver regeneration after partial hepatectomy is improved in the absence of aryl hydrocarbon receptor

“…To study potential mechanisms through which Ahr could participate in liver regeneration after PHx, we next analyzed cytokines known to be involved in the inflammatory response taking place at the initial stages of liver regrowth 27 , 28 . Tnfα and Il6 mRNA expression were transiently upregulated at early time points (e.g.…”

“…Acute inflammation induced after liver surgery also triggers cell cycle entry 28 . Kupffer cells secrete TNF-α and IL6 during the “priming phase” of regeneration 54 , which induce multiple genes coding for acute phase proteins that facilitate the proliferation of hepatocytes 5 .…”

Liver regeneration in traditional Chinese medicine: advances and challenges

“…Notably, recent studies have concentrated on determining the contribution of expansion of the putative hepatic progenitor cell population resident in the bile ductules. It appears that when the ability of hepatocytes to proliferate is inhibited or overwhelmed, the liver maintains the ability to regenerate via mobilization of a population of hepatic progenitor cells [15,16]. For example, in the zebrafish models, where hepatocytes are ablated or prevented from entering the cell cycle, hepatic progenitor cells are activated, proliferate and can restore the hepatocyte mass ensuring survival of the organism [17].…”