MEF2D Aggravates Hepatic Ischaemia-Reperfusion Injury by Transcriptionally Regulating CXCL1 Through Interacting With...

Area of Science:

• Hepatology
• Immunology
• Molecular Biology

Background:

• Hepatic ischemia-reperfusion injury (IRI) is a significant complication following liver surgery and transplantation.
• Myocyte enhancer factor-2D (MEF2D) is implicated in immune responses and hepatic disorders, but its role in IRI remains undefined.

Purpose of the Study:

• To investigate the role and mechanism of MEF2D in hepatic IRI.
• To explore MEF2D as a potential therapeutic target for liver IRI.

Main Methods:

• MEF2D expression was measured in human and mouse liver tissues and hepatocytes undergoing hypoxia/reoxygenation.
• Liver injury, inflammation, and apoptosis were assessed in wild-type and hepatocyte-specific MEF2D knockout mice subjected to IRI.
• Interactions between MEF2D and NAT10, and the effect of NAT10 inhibition on IRI were examined.

Main Results:

• MEF2D expression was upregulated in hepatic IRI in humans and mice, correlating with poor liver transplant outcomes.
• MEF2D deficiency attenuated liver injury, inflammation, and apoptosis in IRI models.
• MEF2D interacts with NAT10, leading to MEF2D acetylation and increased CXCL1 transcription, exacerbating IRI. NAT10 inhibition ameliorated IRI.

Conclusions:

• NAT10-mediated MEF2D acetylation promotes hepatic IRI by upregulating CXCL1 in hepatocytes.
• Targeting the NAT10-MEF2D pathway presents a promising therapeutic avenue for hepatic IRI.