Liver regeneration observed across the different classes of vertebrates from an evolutionary perspective

Abstract

The liver is a key organ that performs diverse functions such as metabolic processing of nutrients or disposal of dangerous substances (xenobiotics). Accordingly, it seems to be protected by several mechanisms throughout the life of organisms, one of which is compensatory hyperplasia, also known as liver regeneration. This review is a recapitulation of the scientific reports describing the different ways in which the various classes of vertebrates deal with liver injuries, where since mammals have an improved molecular toolkit, exhibit optimized regeneration of the liver compared to lower vertebrates. The main molecules involved in the compensatory process, such as proinflammatory and inhibitory cytokines, are analyzed across vertebrates with an evolutionary perspective. In addition, the possible significance of this mechanism is discussed in the context of the long life span of vertebrates, especially in the case of mammals.

The Aging Human Liver: The Weal and Woe of Evolutionary Legacy

“…All of these signals highly relevant in regulating hepatic regeneration evolved at least 550 million years ago [7]. Thus, we come full circle with the separation of invertebrates and vertebrates from their common ancestor mentioned above.…”

“…Finally, transforming growth factor β (TGF-β)which has been around since the emergence of metazoans [46,47] plays a key role in the termination phase of liver regeneration [7]. In this conclusive phase, TGF-β represses urokinase activity, inhibits hepatocyte proliferation, and induces apoptosis, which collectively resets the hepatocytes to quiescence [21,48].…”

“…In this conclusive phase, TGF-β represses urokinase activity, inhibits hepatocyte proliferation, and induces apoptosis, which collectively resets the hepatocytes to quiescence [21,48]. Moreover, the Wnt/ β-catenin pathway (wherein Wnt stands for 'Wingless-related integration site' or 'Wingless/Int-1', respectively), which has remained highly conserved throughout invertebrate and vertebrate evolution [49], is involved both in priming and termination [7]. Thus, this pathway obviously serves as an 'overarching theme' in the orchestration of liver regeneration.…”

The Influence of Interdisciplinary Work towards Advancing Knowledge on Human Liver Physiology

“…Together, this knowledge supports the notion that liver regeneration evolved as an adaptive response to liver injury [ 44 ]. Regardless of their size, all known vertebrate models have contributed to advance the knowledge related to liver regeneration, starting with the zebrafish, which shares not only a high proportion of orthologous genes with the human, but some of the cell plasticity mechanisms that the liver displays after severe damage [ 45 ].…”

Genetic, epigenetic, and post‐transcriptional basis of divergent tissue regenerative capacities among vertebrates

“…Although more complex vertebrates exhibit limited regenerative potential overall, most, if not all, are capable of liver regeneration 79 . Upon partial hepatectomy, the liver undergoes both hyperplasia and hypertrophy to regenerate and restore homeostasis 80,81 .…”