Dynamic and Coordinated Regulation of KEAP1-NRF2-ARE and p53/p21 Signaling Pathways Is Associated with Acetaminophen Injury Responsive Liver Regeneration

It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2–12 h in dendritic cells may be triggered by CCL2–CCR2 and CCL7–CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2–12 h in sinusoidal endothelial cells might be caused by CCL7–CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.

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Coordinated Regulation of Signaling Pathways during Macrophage Activation

Myeloid Cells in Health and Disease ◽

10.1128/9781555819194.ch29 ◽

2017 ◽

pp. 543-552

Author(s):

Toby Lawrence

Keyword(s):

Signaling Pathways ◽

Macrophage Activation ◽

Coordinated Regulation

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Gene expression profiles predict the possible regulatory role of OPN-mediated signaling pathways in rat liver regeneration

Gene ◽

10.1016/j.gene.2015.11.008 ◽

2016 ◽

Vol 576 (2) ◽

pp. 782-790 ◽

Cited By ~ 6

Author(s):

Gaiping Wang ◽

Shasha Chen ◽

Congcong Zhao ◽

Xiaofang Li ◽

Ling Zhang ◽

...

Keyword(s):

Gene Expression ◽

Liver Regeneration ◽

Signaling Pathways ◽

Rat Liver ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Regulatory Role ◽

Rat Liver Regeneration

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Update on the Mechanisms of Liver Regeneration

Seminars in Liver Disease ◽

10.1055/s-0037-1601351 ◽

2017 ◽

Vol 37 (02) ◽

pp. 141-151 ◽

Cited By ~ 27

Author(s):

Morgan Preziosi ◽

Satdarshan Monga

Keyword(s):

Cell Proliferation ◽

Liver Regeneration ◽

Signaling Pathways ◽

Surgical Resection ◽

Molecular Basis ◽

Cell Types ◽

Hepatic Cell ◽

Restoration Process

AbstractLiver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Although the exact mechanisms that initiate regeneration are unknown, alterations in hemodynamics and metabolism have been suspected as important effectors. Key signaling pathways are activated that drive cell proliferation in various hepatic cell types through autocrine and paracrine mechanisms. Once the prehepatectomy mass is regained, the process of regeneration is adequately terminated. This review highlights recent discoveries in the cellular and molecular basis of liver regeneration.

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Regulation of Signal Transduction and Role of Platelets in Liver Regeneration

International Journal of Hepatology ◽

10.1155/2012/542479 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Takeshi Nowatari ◽

Kiyoshi Fukunaga ◽

Nobuhiro Ohkohchi

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Liver Regeneration ◽

Signaling Pathways ◽

Phosphatidyl Inositol ◽

Liver Sinusoidal Endothelial Cells ◽

Necrosis Factor Alpha ◽

Nonparenchymal Cells ◽

Factor Alpha ◽

Regeneration Capability

Among all organs, the liver has a unique regeneration capability after sustaining injury or the loss of tissue that occurs mainly due to mitosis in the hepatocytes that are quiescent under normal conditions. Liver regeneration is induced through a cascade of various cytokines and growth factors, such as, tumor necrosis factor alpha, interleukin-6, hepatocyte growth factor, and insulin-like growth factor, which activate nuclear factorκB, signal transducer and activator of transcription 3, and phosphatidyl inositol 3-kinase signaling pathways. We previously reported that platelets can play important roles in liver regeneration through a direct effect on hepatocytes and collaborative effects with the nonparenchymal cells of the liver, including Kupffer cells and liver sinusoidal endothelial cells, which participate in liver regeneration through the production of various growth factors and cytokines. In this paper, the roles of platelets and nonparenchymal cells in liver regeneration, including the associated cytokines, growth factors, and signaling pathways, are described.

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Expressions Profiles of the Proteins Associated with Carbohydrate Metabolism in Rat Liver Regeneration

BioMed Research International ◽

10.1155/2017/8428926 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Li Yin ◽

Cuifang Chang ◽

Cunshuan Xu

Keyword(s):

Liver Regeneration ◽

Signaling Pathways ◽

Carbohydrate Metabolism ◽

Motif Discovery ◽

Critical Role ◽

Remnant Liver ◽

Absolute Quantitation ◽

New Thinking ◽

Isobaric Tags ◽

First Time

Liver has a very amazing ability to regenerate from the remnant liver after injury or partial hepatectomy (PH). Carbohydrate metabolism plays a critical role in regeneration. Many signaling pathways are involved in the metabolism process. We analyzed the changes of proteins at 0–36 h after PH in rats using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS-based quantitative proteomics strategy. The results showed that 110 proteins and 5 signaling pathways related to carbohydrate metabolism in rat LR changed significantly. Based on a motif discovery method performed by iRegulon, we identified for the first time that the transcription factor SPIB whose motif was enriched among the differentiated genes associated with carbohydrate metabolism may play an important role in liver regeneration for the first time. The findings of this research provide a molecular basis for further unrevealing the mechanism of regeneration at priming stage (0–6 h) and proliferation stage (6–36 h) of LR in rats. At the same time, our studies provide more novel evidence for the signaling pathways which regulate carbohydrate metabolism from proteomics level. This study can provide some new thinking of liver regeneration and treatment of diseases associated with glucose metabolism.

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