Understanding Of Liver Regeneration Research Articles

Expression profiles of lncRNAs, miRNAs, and mRNAs during the proliferative phase of liver regeneration in mice with liver fibrosis

The role of lncRNAs in the regeneration of fibrotic liver is unclear. To address this issue, we established a 70% hepatectomy model of liver fibrosis in mice, used high-throughput sequencing technology to obtain the expression profiles of lncRNAs, miRNAs, and mRNAs, and constructed a lncRNA–miRNA–mRNA regulatory network. A total of 1329 lncRNAs, 167 miRNAs, and 6458 mRNAs were differentially expressed. On this basis, a lncRNA–miRNA–mRNA ceRNA regulatory network consisting of 38 DE lncRNAs, 24 DE miRNAs, and 299 DE mRNAs was constructed, and a transcription factor (TF) – mRNA regulatory network composed of 20 TFs and 98 DE mRNAs was built. Through the protein network analysis, a core protein interaction network composed of 20 hub genes was derived. Furthermore, Xist/miR-144-3p/Cdc14b and Snhg3/miR-365-3p/Map3k14 axes in the ceRNA regulatory network were verified by Real-Time quantitative PCR. Therefore, we concluded that these new insights may further our understanding of liver regeneration.

Molecular pathways of liver regeneration: A comprehensive review.

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70% of its volume. Although knowledge of this phenomenon dates back to Greek mythology (the story of Prometheus), many aspects of liver regeneration are still not understood. A variety of different factors, including inflammatory cytokines, growth factors, and bile acids, promote liver regeneration and control the final size of the organ during typical regeneration, which is performed by mature hepatocytes, and during alternative regeneration, which is performed by recently identified resident stem cells called “hepatic progenitor cells”. Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass, such as in cases of chronic injury or excessive acute injury. In liver maintenance, the body mass ratio is essential for homeostasis because the liver has numerous functions; therefore, a greater understanding of this process will lead to better control of liver injuries, improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases. The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries. Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.

Liver regeneration in traditional Chinese medicine: advances and challenges.

Liver diseases pose a serious problem for national health care system all over the world. Liver regeneration has profound impacts on the occurrence and development of various liver diseases, and it remains an extensively studied topic. Although current knowledge has suggested two major mechanisms for liver regeneration, including compensatory hyperplasia of hepatocytes and stem or progenitor cell-mediated regeneration, the complexity of this physiopathological process determines that its effective regulation cannot be achieved by single-target or single-component approaches. Alternatively, using traditional Chinese medicine (TCM) to regulate liver regeneration is an important strategy for prevention and treatment of liver disorder and the related diseases. From the perspectives of TCM, liver regeneration can be caused by the disrupted balance between hepatic damage and regenerative capacity, and the “marrow”-based approaches have important therapeutic implications for liver regeneration. These two points have been massively supported by a number of basic studies and clinical observations during recent decades. TCM has the advantages of overall dynamic fine-tuning and early adjustment, and has exhibited enormous therapeutic benefits for various liver diseases. Here, we review the recent advances in the understanding of liver regeneration in TCM system in the hope of facilitating the application of TCM for liver diseases via regulation of liver regeneration.

Unexpected finding provides new understanding of liver regeneration

Unexpected finding provides new understanding of liver regeneration

Auxiliary liver transplantation in children

Auxiliary liver transplantation (ALT) has developed as a technique for treating patients with acute liver failure. The surgical techniques of ALT have been refined and current patient survival appears to be similar to that observed with conventional liver replacement for acute liver failure. Our understanding of liver regeneration has improved with experience and it is possible to identify patient and disease groups that are more likely to regenerate and wean off immunosuppression after ALT. Withdrawal of immunosuppression is possible in at least two thirds of survivors up to 4 years post transplant. Young patients have most to gain in the long term from immunosuppression withdrawal. Documentation of liver regeneration should be performed by liver histology, nuclear medicine scanning and CT volumetry. Weaning should be gradual to allow for graft atrophy to avoid complications. ALT has also been utilised for the management of inborn errors of metabolism based in the liver and for other rare problems and these will be briefly addressed in the review. Auxiliary liver transplantation should be considered for the treatment of children with acute liver failure satisfying current criteria for liver transplantation.

Expression of interleukin 6 and apoptosis-related genes in suckling and weaning rat models of hepatectomy and liver regeneration

Background/Purpose The most commonly used model to study the mechanisms of liver regeneration is the adult rat submitted to 70% to 80% hepatectomy. However, there are no studies using newborn or weaning rat models. The process of liver regeneration includes both the hypertrophy and hyperplasia of cells (processes regulated by growth factors and cytokines, mainly interleukin 6 [IL-6]) as well as apoptosis, or programmed cell death (a process regulated mainly by the Bcl-2 family of proteins). Proapoptotic proteins in this family include Bax and Bak. Conversely, Bcl-2 and Bcl-XL are antiapoptotic regulators. Therefore, to expand our understanding of liver regeneration, our study had 2 goals: first, to standardize 2 animal models of hepatectomy and liver regeneration using the newborn suckling and the weaning rat and second, to quantitate the expression levels of IL-6 and several members of the Bcl-2 gene family during the regeneration process. Methods To create the experimental models, newborn suckling rats (age, 5-7 days; weight, 6-10 g) and weaning rats (age, 21-23 days; weight, 30-50 g) underwent 70% hepatectomy. The animals were subsequently sacrificed at days 1, 2, 3, 4, and 7 after hepatectomy, and the remnant liver lobes were harvested for routine histologic examination. Groups of healthy animals not operated on served as controls. For the experimental study, 6 newborn rats and 6 weaning rats underwent hepatectomy. The animals were killed 1 day after liver resection and the remnant livers were harvested to assess gene expression by quantitative reverse transcription-polymerase chain reaction. The hepatectomized groups were compared with control and sham groups. Results During the creation of the experimental models, 70% of the suckling animals and all the weaning animals survived the hepatectomy. The decreased liver weight was completely restored to control levels by day 7 after hepatectomy. Histologically, the remnant livers of both hepatectomy groups exhibited steatosis, tumefaction of hepatocytes, and mitosis, which ceased at 7 days after the hepatectomy. The weaning rat model showed more robust gene expression responses. Specifically, expression levels of IL-6 gene were significantly increased after both surgical insult (sham group) and hepatectomy. However, this increase was significantly higher in the latter group. Furthermore, hepatectomy promoted a decrease in the expression levels of the proapoptotic genes and an increase in the expression levels of Bcl-2. Conclusions Our data indicate that regulation of both IL-6 and genes involved in apoptosis are strongly implicated in the mechanisms of liver regeneration and that the weaning rat model represents an attractive model system for future investigations in this area.