The role of kupffer cells in rat liver regeneration revealed by cell‐specific microarray analysis

Xu, Chi; Jiang, Yun; Zhang, Lian-Xing; Chang, Cuifang; Wang, Gai-Ping; Shi, Runbin; Yang, Yanjie

doi:10.1002/jcb.23348

Cited by 27 publications

(19 citation statements)

References 26 publications

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“…As the persistent infection proceeded, a large area of hepatocyte damage, which would translate to liver damage in an animal model, was observed (Fig 7). Our simulated results paralleled hepatocyte damage seen in vivo after experimental infections where recovery (or “healing”) of hepatocytes was detected after 7 days and continued for approximately 30 days [120]. These data are consistent with the idea that a persistent infection will induce a higher mortality rate compared to a healing response because acute tissue damage is more detrimental to the host (Fig 6B).…”

Section: Resultssupporting

confidence: 87%

“…However, if the initial Salmonella load was high, a hyperinflammatory response or organ dysfunction was most likely to occur, leading to the death of infected individuals. In addition, when these simulated results were compared to experimental data, the simulations paralleled indicator patterns reported in actual mouse experiments [112, 115, 116, 118–120, 122]. It also became clear that predicting a final outcome from the emerging dynamic patterns of HIR became more difficult when initial Salmonella loads were above 500 counts (See Section 3.4).…”

Section: Resultsmentioning

confidence: 53%

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An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

et al. 2016

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We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as “sepsis”. Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-α ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 53%

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

et al. 2016

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“…Peak macrophage proliferative response is at 48–72h [80], at which point they begin to communicate with hepatocytes mostly through the production of IL-6 [81, 82]. LSEC and HSC divide approximately 96h after partial hepatectomy, primarily due to hepatocyte-derived VEGF/angiopoietin stimulation, and proteins relying on phosphoinositide 3-kinase for their mitogenic effect, respectively [83–85].…”

Section: - Sinusoidal Crosstalk In Liver Regeneration and Transplantmentioning

confidence: 99%

Sinusoidal communication in liver fibrosis and regeneration

Marrone

Shah

Gracia‐Sancho

2016

Journal of Hepatology

261

208

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Cellular crosstalk is a process through which a message is transmitted within an individual cell (intracellular crosstalk) or between different cells (intercellular crosstalk). Intercellular crosstalk within the liver microenvironment is critical for the maintenance of normal hepatic functions and for cells survival. Hepatic cells are closely connected to each other, work in synergy, and produce molecules that modulate their differentiation and activity. This review summarises the current knowledge regarding paracrine communication networks in parenchymal and non-parenchymal cells in liver fibrosis due to chronic injury, and regeneration after partial hepatectomy.

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“…Most recently, a growing body of evidence suggests that the beneficial effect of EPO treatment on liver resection and living donor liver transplantation in rats [14,[17][18]. Moreover, microarray analysis is a powerful approach for monitoring molecular events during liver regeneration after PH, which has been demonstrated in previous studies [24,25,[33][34][35][36][37][38][39][45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy

Zhang

Yang

et al. 2014

Cellular and Molecular Biology Letters

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Erythropoietin (EPO) has a beneficial effect on hepatic cell proliferation during liver regeneration. However, the underlying mechanism has not yet been elucidated. To uncover the proliferation response of EPO in rat liver regeneration after partial hepatectomy (PH) at the cellular level, hepatocytes (HCs) were isolated using Percoll density gradient centrifugation. The genes of the EPO-mediated signaling pathway and the target genes of the transcription factor (TF) in the pathway were identified in a pathway and TF database search. Their expression profiles were then detected using Rat Genome 230 2.0 Microarray. The results indicated that the EPO-mediated signaling pathway is involved in 19 paths and that 124 genes participate, of which 32 showed significant changes and could be identified as liver regeneration-related genes. In addition, 443 targets regulated by the TFs of the pathway and 60 genes associated with cell proliferation were contained in the array. Subsequently, the synergetic effect of these genes in liver regeneration was analyzed using the E(t) mathematical model based on their expression profiles. The results demonstrated that the E(t) values of paths 3, 8, 12 and 14–17 were significantly strengthened in the progressing phase of liver regeneration through the RAS/MEK/ERK or PI3K/AκT pathways. The synergetic effect of the target genes, in parallel with target-related cell proliferation, was also enhanced 12–72 h after PH, suggesting a potential positive effect of EPO on HC proliferation during rat liver regeneration. These data imply that the EPO receptor may allow EPO to promote HC proliferation through paths 3, 8, 12 and 14–17, mediating the RAS/MEK/ERK and PI3K/AκT pathways in rat liver regeneration after PH.

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The role of kupffer cells in rat liver regeneration revealed by cell‐specific microarray analysis

Cited by 27 publications

References 26 publications

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Sinusoidal communication in liver fibrosis and regeneration

Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy

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