The molecular physiology of liver regeneration following partial hepatectomy

Abstract

The ability of the liver to regenerate after resection has been known for many years. Two reports from Germany in the late 1800s probably mark the introduction of the phenomenon into the scientific literature, but in the early 1900s the first reviews of this subject had appeared in the English literature. Predating these early scientific reports the legends from the Greek mythology described the fate of Prometheus. As punishment for defying Zeus and revealing the secret of fire to man, Prometheus was chained to a rock and each day had part of his liver ripped out by an eagle which, returning the following day, repeated the torture because his liver regenerated itself overnight. Although the speed of regeneration in the Greek legend is somewhat greater than that observed either clinically or in the laboratory, the myth does serve to emphasise the remarkable ability of the liver to repeatedly regenerate following repeated resections. This review aims to summarise the more recent literature concerning the early molecular events accompanying liver regeneration and to integrate this with the existing knowledge of this subject.

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

“…Since the state of histone H2A ubiquitylation changes robustly in concert with hepatic regeneration and its concomitant gene regulation network, regenerating liver chromatin provides a superb model to study gene regulation by ubH2A (Michalopoulos and DeFrances 1997;Costa et al 2003;Mangnall et al 2003;Fausto et al 2006). Within this network, the monoubiquitylation of core histone H2A dynamically changes, with the bulk of this modification decreasing during hepatocyte regeneration (Fig.…”

“…Following a two-thirds hepatectomy, normally quiescent hepatocytes undergo one or two rounds of replication to restore the liver mass by a process of compensatory hyperplasia. A large number of genes comprises the gene expression network that is associated with liver regeneration (for reviews, see Michalopoulos and DeFrances 1997;Costa et al 2003;Mangnall et al 2003;Fausto et al 2006).…”

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

“…In the human genome, STAT1 and STAT4 are clustered on chromosome 2, whereas STAT3, STAT5a, and STAT5b are huddled together on chromosome 17, and STAT2 and STAT6 are assembled on chromosome 12 [44,46]. Among other STAT family proteins, STAT3 has received considerable attention during the last decade since it is a convergent point for a number of oncogenic signaling pathways and controls intra-cellular signal transduction pathways of several pro-inflammatory cytokines and growth factors that are implicated in liver damage and repair mechanisms [47][48][49][50]. STAT3 was initially identified as an acute phase response factor (APRF), an inducible DNA binding protein that binds to the IL-6 responsive element within the promoters of hepatic acute phase genes [51] and as a DNA binding protein in response to epidermal growth factor [52].…”

Regeneração do fígado de ratos após oclusão parcial da drenagem venosa hepática

“…De forma consensual, é aceito que a regeneração hepática humana é similar a de roedores, porém com diferenças temporais nas respostas ao estímulo inicial, a hepatectomia parcial 14 . No ser humano ainda não foram estabelecidos os tempos necessários a cada etapa, contudo evidências sugerem que haja rápida regeneração nas primeiras duas semanas, e a seguir gradual aumento de tamanho até cessar em torno de seis a 12 meses, quando o fígado tenha restaurado aproximadamente 75% de sua massa original.…”