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Short-term effects of overexpression of GK and/or GKRP on the transcriptome in mouse primary hepatocytes

ABSTRACT: Short-term effects of overexpression of GK and/or GKRP on the transcriptome in mouse primary hepatocytes

PROVIDER: PRJNA951223 | ENA |

REPOSITORIES: ENA

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Short-term effects of overexpression of GK and/or GKRP on the transcriptome in mouse primary hepatocytes

Project description:Short-term effects of overexpression of GK and/or GKRP on the transcriptome in mouse primary hepatocytes

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RNA-seq transcriptional profiling in primary human hepatocytes, short- and long-term cultured Proliferating human hepatocytes (in vitro/in vivo)

Project description:One of the major challenges of cell therapy is manufacturing of the effective seed cells, which inevitably requires the expansion of cells in vitro. Although considerable progresses have been achieved in expansion of primary human hepatocytes (PHH) in vitro, the transplantation efficiency of proliferating human hepatocytes was decreased with the extended culture. The mechanism of declined transplantation is not clear.Here, we found that long-term cultured proliferating human hepatocytes (lc-ProliHH) significantly upregulated chemokines and proinflammatory cytokines associated with innate immune response. Moreover, lc-ProliHH elicited robust recruitment of macrophages and neutrophils at early stage of transplantation, and being cleared by macrophages caused the engraftment efficiency reduction.Based on these findings, we designed to treat recipient with Dexamethasone (Dex), which decreased the response of innate immune cells and significantly increased the transplantation efficiency to a level approximate to PHH in the liver-injured mice. Furthermore, ProliHH organoid reduced the expression of cytokine genes and behaved close to mature hepatocyte, and as a result, ameliorated their transplantation efficiency as well.

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The effect of TRIB3 overexpression on mouse hepatocytes

Project description:To investigate the effect of TRIB3 overexpression on regulation of lipid metabolism in hepatocytes, we isolated mouse primary hepatocytes from AAV-GFP or AAV-Trib3 mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of two groups of mouse primary hepatocytes from AAV-GFP or AAV-Trib3 mice.

2023-05-28 | GSE232807 | GEO

Cardioprotective signature of short-term caloric restriction

Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. .

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Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes and Can be Partially Reversed by Antiviral Therapy

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2021-08-31 | PXD028190 |

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