scholarly journals Liver Regeneration: Analysis of the Main Relevant Signaling Molecules

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yachao Tao ◽  
Menglan Wang ◽  
Enqiang Chen ◽  
Hong Tang
Keyword(s):  
Growth Factors ◽  
Liver Regeneration ◽  
Normal Liver ◽  
Initial Step ◽  
Signaling Molecules ◽  
Regenerative Process ◽  
Liver Mass ◽  
Termination Phase ◽  
And Function ◽  
Stimulation Of

Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of liver regeneration includes three phases: priming stage, proliferative phase, and termination phase. The initial step aims to induce hepatocytes to be sensitive to growth factors with the aid of some cytokines, including TNF-α and IL-6. The proliferation phase promotes hepatocytes to re-enter G1 with the stimulation of growth factors. While during the termination stage, hepatocytes will discontinue to proliferate to maintain normal liver mass and function. Except for cytokine- and growth factor-mediated pathways involved in regulating liver regeneration, new substances and technologies emerge to influence the regenerative process. Here, we reviewed novel and important signaling molecules involved in the process of liver regeneration to provide a cue for further research.

scholarly journals Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form

1988 ◽  
Vol 251 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G L Francis ◽  
F M Upton ◽  
F J Ballard ◽  
K A McNeil ◽  
J C Wallace
Keyword(s):  
Growth Factors ◽  
Biological Activities ◽  
Structure And Function ◽  
Bovine Colostrum ◽  
Amino Acid Sequences ◽  
Truncated Form ◽  
Reverse Phase ◽  
And Function ◽  
Stimulation Of ◽  
Insulin Like Growth Factors

1. Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) together with a truncated form of IGF-1 were purified to homogeneity from bovine colostrum. 2. Two forms of IGF-1 were totally resolved from IGF-2 in the purification by h.p.l.c. involving cation-exchange and reverse-phase columns. 3. The complete amino acid sequences for all three forms of IGF were determined. The sequence of bovine IGF-1 was found to be identical with that of human IGF-1, and that of the variant lacked the N-terminal tripeptide Gly-Pro-Glu (-3N:IGF-1). Bovine IGF-2 was found to differ in three residues of the C-domain compared with human IGF-2, with serine, isoleucine and asparagine substituted for alanine, valine and serine respectively at positions 32, 35 and 36. 4. Protein synthesis in L6 rat myoblasts was stimulated and protein degradation inhibited in a co-ordinate response with all three IGFs. The relative potency in both processes was −3N:IGF-1 greater than IGF-1 greater than IGF-2. A similar order of potency was obtained for the stimulation of DNA synthesis by −3N:IGF-1 and IGF-1. The approximately 10-fold effect on biological activity of removing the N-terminal tripeptide is unexpected in view of current information on IGF-1 structure and function.

scholarly journals Large-Scale Profiling of Signaling Pathways Reveals a Distinct Demarcation between Normal and Extended Liver Resection

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1149
Author(s):  
Pieter Borger ◽  
Anton Buzdin ◽  
Maksim Sorokin ◽  
Ekaterina Kachaylo ◽  
Bostjan Humar ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Signaling Pathways ◽  
Liver Tissue ◽  
Intracellular Signaling ◽  
Large Scale ◽  
Transcriptome Profiling ◽  
Normal Liver ◽  
Regenerative Process ◽  
Intracellular Signaling Pathways ◽  
Genome Wide

Despite numerous studies addressing normal liver regeneration, we still lack comprehensive understanding of the biological processes underlying failed liver regeneration. Therefore, we analyzed the activity of 271 intracellular signaling pathways (ISPs) by genome wide profiling of differentially expressed RNAs in murine liver tissue biopsies after normal hepatectomy (nHx; 68% of liver removed) and extended hepatectomy (eHx; 86% of liver removed). Comprehensive, genome-wide transcriptome profiling using RNAseq was performed in liver tissue obtained from mice (sham, nHx, and eHx) harvested 1, 8, 16, 32, and 48 h after operation (n = 3 per group) and the OncoFinder toolkit was used for an unsupervised, unbiased identification of intracellular signaling pathways (ISP) activity. We observed that the normal regenerative process requires a transient activation and silencing of approximately two dozen of ISPs. After nHx, the Akt Pathway represented with 13 branches, the Chromatin Pathway and the DDR Pathways dominated. After eHx, the ATM main pathway and two of its branches (Cell Survival; G2_M Checkpoint Arrest) dominated, as well as the Hypoxia Pathways. Further, 14 ISPs demonstrated a strong inverse regulation, with the Hedgehog and the Brca1 Main Pathways as chief activators after nHx, and the ATM Pathway(G2_M Checkpoint Arrest) as the dominating constraining response after eHx.

scholarly journals A molecular view of liver regeneration

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 58-62 ◽  
Author(s):  
Marissa Rabelo Tarlá ◽  
Fernando Silva Ramalho ◽  
Leandra Naira Zambelli Ramalho ◽  
Tiago Castro e Silva ◽  
Daniel Ferracioli Brandão ◽  
...  
Keyword(s):  
Growth Factors ◽  
Liver Regeneration ◽  
Cellular Membrane ◽  
Regenerative Process ◽  
Hepatic Tissue ◽  
Scientific Publications ◽  
New Approach ◽  
Cellular Processes ◽  
Mechanism Of Interaction ◽  
Mitogenic Potential

The purpose of this review was to carry out an analysis of the liver regenerative process focusing on the molecular interactions involved in this process. The authors undertook a review of scientific publications with a focus on the liver regeneration.The cellular processes involved in liver regeneration require multiple systematic actions related to cytokines and growth factors. These interactions result in the initiation of mitogenic potential of the hepatocytes. The action of these modulators in the regenerative process require a processing in the extra-cellular matrix. Serines and metal proteins are responsible for the bio availability of cytokines and growth factors so that they can interact as receptors in the cellular membrane generating signaling events for the beginning and end of the liver regenerative process. The exact mechanism of interaction between cells, cytokines and growth factors is not well established yet. A series of ordered events that result in the hepatic tissue regeneration has been described. The better understanding of these interactions should provide a new approach of the treatment for liver diseases, aiming at inducing the regenerative process.

Bile Acids and Stellate Cells

2015 ◽  
Vol 33 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Claus Kordes ◽  
Iris Sawitza ◽  
Silke Götze ◽  
Dieter Häussinger
Keyword(s):  
Liver Regeneration ◽  
Bile Acids ◽  
Hepatic Stellate Cells ◽  
Normal Liver ◽  
Stellate Cells ◽  
Hepatic Differentiation ◽  
Liver And Pancreas ◽  
And Function

Hepatic stellate cells are mainly known for their contribution to fibrogenesis in chronic liver diseases, but their identity and function in normal liver remain unclear. They were recently identified as liver-resident mesenchymal stem cells (MSCs), which can differentiate not only into adipocytes and osteocytes, but also into liver epithelial cells such as hepatocytes and bile duct cells as investigated in vitro and in vivo. During hepatic differentiation, stellate cells and other MSCs transiently develop into liver progenitor cells with epithelial characteristics before hepatocytes are established. Transplanted stellate cells from the liver and pancreas are able to contribute to liver regeneration in stem cell-based liver injury models and can also home into the bone marrow, which is in line with their classification as MSCs. There is experimental evidence that bile acids support liver regeneration and are able to activate signaling pathways in hepatic stellate cells. For this reason, it is important to analyze the influence of bile acids on developmental fate decisions of hepatic stellate cells and other MSC populations.

scholarly journals MicroRNAs in Liver Regeneration

2015 ◽  
Vol 37 (2) ◽  
pp. 615-628 ◽  
Author(s):  
Xiaoyu Chen ◽  
Yingying Zhao ◽  
Fei Wang ◽  
Yihua Bei ◽  
Junjie Xiao ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Growth Factors ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Regenerative Process ◽  
Hepatocyte Proliferation ◽  
Regeneration Capacity ◽  
Regulatory Effects

Liver maintains a unique tremendous regeneration capacity in response to partial hepatectomy (PH) or injury. Hepatocyte proliferation critically contributes to the process of liver regeneration (LR), which is regulated by various cytokines and growth factors. However, the molecular basis of LR remains unclear. Emerging evidence indicates that microRNAs (miRNAs, miRs) are involved in controlling hepatocyte proliferation during LR. In this review, an overview is provided to cover recent achievements in studies on the roles of miRNAs in LR. Studies on the regulatory effects of miRNAs and associated molecular mechanisms in LR will help enhance the understanding of the regenerative process and open up a new prospect for liver transplantation.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3.

1987 ◽  
Vol 84 (9) ◽  
pp. 2761-2765 ◽  
Author(s):  
A. F. Lopez ◽  
L. B. To ◽  
Y. C. Yang ◽  
J. R. Gamble ◽  
M. F. Shannon ◽  
...  
Keyword(s):  
Human Cells ◽  
Interleukin 3 ◽  
And Function ◽  
Stimulation Of

914 Heparanase expression during normal liver development and liver regeneration following partial hepatectomy

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 598-598
Author(s):  
O GOLDSHMIDT ◽  
R YEIKILIS ◽  
M PAIZI ◽  
I VLODAVSKY ◽  
G SPIRA
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Normal Liver ◽  
Liver Development

Trans-dentinal Stimulation of Tertiary Dentinogenesis

2001 ◽  
Vol 15 (1) ◽  
pp. 51-54 ◽  
Author(s):  
A.J. Smith ◽  
P.E. Murray ◽  
A.J. Sloan ◽  
J.B. Matthews ◽  
S. Zhao
Keyword(s):  
Growth Factors ◽  
Tissue Injury ◽  
Careful Consideration ◽  
Active Components ◽  
Restorative Treatment ◽  
Cellular Events ◽  
Dentin Matrix ◽  
Dentin Thickness ◽  
Tertiary Dentinogenesis ◽  
Stimulation Of

Trans-dentinal stimulation of tertiary dentinogenesis has long been recognized, and has traditionally been ascribed to diffusion of irritant substances arising during injury and restorative treatment. Identification of bio-active components, especially growth factors including TGF-βs, sequestered within dentin matrix provides a new explanation for cellular signaling during tertiary dentinogenesis. Both isolated dentin matrix components and pure growth factors (TGF-βs) have been shown to signal cellular events leading to reactionary and reparative tertiary dentinogenesis. Release of these bio-active components from dentin matrix may arise during carious attack and other injury to the tissue, and also during subsequent surgical intervention and restoration of the tooth. Both cavity-conditioning agents and leaching from restorative materials may contribute to release of these components. Distance of diffusion, as determined by cavity residual dentin thickness, and other restorative parameters may influence the signaling process after release of these components. Careful consideration of the interplay between tissue injury and surgical and restorative material factors is required for optimum exploitation of the exquisite regenerative capacity of dentin-pulp for more biological approaches to clinical treatment of dental disease.

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