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Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
MAFF alleviates hepatic ischemia-reperfusion injury by regulating the CLCF1/STAT3 signaling pathway
Dengliang Lei1, Yihua Wang2, Shanshan Li1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
Although hepatic ischemia-reperfusion injury (IRI) frequently occurs during liver resection and transplantation, the underlying mechanisms remain incompletely understood. Through high-throughput sequencing, we found that v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) expression was significantly increased after hepatic IRI. The specific role of MAFF, a basic leucine zipper (bZIP) transcription factor, in hepatic IRI is unknown. In the present study, we aimed to explore the effect of MAFF on hepatic IRI injury.
Approach And Results:
Adenovirus vectors carrying the MAFF gene were administered to mice to explore the potential significance of MAFF. After ischemia-reperfusion, MAFF expression was significantly upregulated, suggesting a potential association between MAFF expression and hepatocyte apoptosis. A reduction in MAFF expression was demonstrated to worsen hepatic impairment and enhance the expression of proinflammatory cytokines in mice following ischemia-reperfusion. Conversely, MAFF overexpression had the opposite effect. Mechanistically, the combination of CUT&Tag and RNA sequencing technologies identified cardiotrophic factor-like cytokine 1 (CLCF1) as a direct transcriptional target for MAFF and BTB and CNC homology 1 (BACH1) heterodimers. This interaction subsequently triggers signal transducer and activator of transcription 3 (STAT3) signaling.
Conclusions:
MAFF alleviates hepatic ischemia-reperfusion injury by reducing hepatocyte apoptosis and the inflammatory response through the activation of the CLCF1/STAT3 signaling pathway, offering valuable insights into the impact of MAFF on liver protection and potential therapeutic targets for liver treatment.
Insights
MAFF protects the liver from ischemia-reperfusion injury by reducing cell death and inflammation. This transcription factor activates the CLCF1/STAT3 pathway, offering potential therapeutic strategies for liver treatment.
Area of Science:
- Hepatology
- Molecular Biology
- Immunology
Background:
- Hepatic ischemia-reperfusion injury (IRI) is a common complication during liver surgery and transplantation.
- The molecular mechanisms underlying hepatic IRI are not fully understood.
- v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) expression is upregulated after hepatic IRI.
Purpose of the Study:
- To investigate the role of MAFF in hepatic IRI.
- To explore the therapeutic potential of MAFF in liver protection.
Main Methods:
- Adenovirus vectors were used to manipulate MAFF expression in mice.
- High-throughput sequencing and CUT&Tag/RNA sequencing were employed.
- Analysis of hepatocyte apoptosis and proinflammatory cytokine expression.
Main Results:
- MAFF expression is upregulated following ischemia-reperfusion.
- Reduced MAFF expression exacerbates hepatic injury and inflammation.
- MAFF overexpression ameliorates hepatic IRI.
- MAFF, via BACH1 heterodimers, directly targets CLCF1, activating STAT3 signaling.
Conclusions:
- MAFF alleviates hepatic IRI by reducing hepatocyte apoptosis and inflammation.
- The protective effect of MAFF is mediated through the CLCF1/STAT3 signaling pathway.
- MAFF represents a potential therapeutic target for liver protection.
