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Updated: Jun 13, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Analysis of gene expression profiles in fatal hepatic failure after hepatectomy in mice
Hirochika Makino1, Hiroshi Shimada, Daisuke Morioka
1Department of Gastroenterological Surgery, Yokohama City University School Graduate of Medicine, Yokohama, Japan. hirochik@urahp.yokohama-cu.ac.jp
Background:
We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy.
Materials And Methods:
Ribonucleic acid (RNA)s from the remnant hepatic tissue of 70%- and 90%-hepatectomized mice were labeled with fluorescent dyes, and hybridized to the Riken set of 39,168 full-length enriched mouse cDNA arrays. The gene expression profiles in 90%- and 70%-hepatectomized mice were analyzed by scanning date for fluorescent dye signals.
Results:
The down-regulated genes in 90%-hepatectomized mice were genes activating extracellular matrix (ECM) remodeling (matrix metalloproteinases, laminins, and integrins), genes related to cytokines (tumor necrosis factor α converting enzyme, and Janus kinase 3) that were related to the priming, genes related to growth factor (heparin-binding epidermal growth factor-like growth factor and others), and genes promoting cell cycle progression (cyclin D1, D2, and E2) that were related to the progression of hepatocytes. The up-regulated genes were genes inhibiting ECM remodeling [plasminogen activator inhibitors (PAIs)].
Conclusions:
Hepatic failure after hepatectomy was characterized by the inhibition of hepatic cell cycle priming and progression both induced by ECM remodeling in liver regeneration. Particularly, the overexpression of PAIs was thought to play the major role in the first step of inhibition of ECM remodeling.
Insights
Excessive hepatectomy in mice leads to liver failure due to inhibited cell cycle progression and extracellular matrix remodeling. Overexpression of plasminogen activator inhibitors (PAIs) significantly contributes to this failure.
Area of Science:
- Molecular Biology
- Genomics
- Hepatology
Background:
- Developed a fatal mouse model of liver failure following 90% hepatectomy.
- Investigated gene expression profiles to understand mechanisms of hepatic failure.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying hepatic failure after excessive hepatectomy.
- To identify key genes and pathways involved in liver regeneration failure.
Main Methods:
- Utilized complementary DNA (cDNA) microarray analysis on remnant hepatic tissue from 70% and 90% hepatectomized mice.
- Analyzed gene expression profiles by hybridizing fluorescently labeled ribonucleic acid (RNA) to a comprehensive mouse cDNA array.
Main Results:
- Down-regulated genes in 90% hepatectomized mice included those involved in extracellular matrix (ECM) remodeling, cytokine signaling, growth factor pathways, and cell cycle progression.
- Up-regulated genes primarily consisted of genes inhibiting ECM remodeling, notably plasminogen activator inhibitors (PAIs).
Conclusions:
- Hepatic failure post-hepatectomy is characterized by suppressed hepatic cell cycle priming and progression, linked to ECM remodeling.
- Overexpression of PAIs plays a critical role in inhibiting ECM remodeling, a key early step in liver regeneration failure.
