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| Status |
Public on Aug 28, 2020 |
| Title |
Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.
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| Overall design |
We have reported that disruption of mitochondrial fission by deletion of Drp1 leads to an alteration in expression of the genes involved in the immune system in the liver and significant elevation of pro-inflammatory cytokines was detected in Drp1 knockout cells. To fully reveal the gene expression altered by Drp1 deletion, we conducted an independent microarray analysis with primary hepatocyte harvested 24 hours after seeding.
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| Contributor(s) |
Wang L, Nomura M |
| Citation(s) |
34290349 |
| Submission date |
Aug 27, 2020 |
| Last update date |
Aug 18, 2021 |
| Contact name |
Lixiang Wang |
| E-mail(s) |
ourika0211@yahoo.co.jp
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| Organization name |
Graduate School of Medical Sciences, Kyushu University
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| Department |
Department of Medicine and Bioregulatory Science
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| Street address |
3-1-1, Maidashi, Higashi-ku
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| City |
Fukuoka |
| State/province |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA659722 |
