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Updated: May 22, 2026
05:53
Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
Mitogen-activated Protein Kinase big Mitogen-activated Kinase-1 Mediates Protection in Liver Ischemia/Reperfusion
Yuan Liu1,2, Aiwei Zhou1,2, Zhipeng Zong1,2
1Division of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Transplantation
|May 21, 2026
Summary
Big mitogen-activated kinase-1 (BMK1) protects the liver from ischemia/reperfusion injury (IRI). BMK1 signaling, involving YAP and KLF4, offers a new therapeutic target for liver transplantation.
Area of Science:
- Hepatology
- Molecular Biology
- Transplantation Immunology
Background:
- Hepatic ischemia/reperfusion injury (IRI) is a significant complication in liver transplantation, shock, and resection.
- Big mitogen-activated kinase-1 (BMK1) is crucial for endothelial cell integrity and organ development.
Purpose of the Study:
- To investigate the role of BMK1 in liver IRI.
- To elucidate the underlying molecular mechanisms of BMK1 in liver protection.
Main Methods:
- Analysis of liver biopsies from human transplant recipients (n=60).
- Murine model of partial warm liver IRI.
- In vivo and in vitro experiments using siRNA, chemical inhibitors, and overexpression of BMK1, YAP, and KLF4.
- Hypoxia-reoxygenation assays and immunofluorescence staining.
Main Results:
- Increased intrahepatic BMK1 expression correlated with better histology and graft function in transplant patients.
- BMK1 inhibition exacerbated liver injury in mice, while BMK1 overexpression conferred protection.
- BMK1-mediated protection involved upregulation and dephosphorylation of YAP, dependent on KLF4.
- BMK1 regulated YAP via itchy E3 ubiquitin ligase-mediated ubiquitination of large tumor suppressor homolog 1.
Conclusions:
- BMK1 signaling plays a critical protective role in the liver against IRI.
- The BMK1-YAP-KLF4 pathway represents a novel therapeutic target to mitigate liver dysfunction in transplantation.
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