A domestic research team has identified a mechanism that improves ischemic liver injury, opening the possibility for drug development.

The research teams led by Professors Eun-Ju Bae and Chang-Yeop Han, School of Pharmacy, Jeonbuk National University (JBNU), in collaboration with the research teams of Professors Byung-Hyun Park and Hee-Chul Yoo, College of Medicine, JBNU, the research team of Professor Kyung-Seok Seo at Seoul National University Hospital, and Dr. Nam‑Doo Kim at Voronoi Bio Co., Ltd., elucidated a mechanism whereby inhibiting p21-activated kinase 4 (PAK4), which increases during ischemic liver injury, alleviates liver damage.

The findings were published in Hepatology (Impact Factor 17.425), a renowned international journal in the field of liver research.

Ischemic liver injury can occur particularly during liver transplantation and directly affects the success of the surgery. It refers to the ischemic state in which blood supply to liver tissue is blocked and the rapid oxidative damage that occurs when blood flow is restored. Although numerous studies worldwide have sought to suppress ischemic liver injury, there has been no clear therapeutic outcome to date.

The research team noted increased PAK4 in the livers of patients who underwent liver transplantation. Using PAK4 gene knockout animal models and animal models treated with a newly developed PAK4 inhibitor, they found that inhibiting PAK4 function improved liver injury.

The research team stated, "It is significant that we have, for the first time, proposed the possibility of developing a new drug that alleviates ischemic liver injury by inhibiting PAK4 function."

Meanwhile, this study was supported by the National New Drug Development Project funded by the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, and the Ministry of Health and Welfare, and by the Leading Research Center (MRC) support program in the medical and pharmaceutical field.

■Paper Title: PAK4 inhibition protects against liver ischemia/reperfusion injury: Role of Nrf2 phosphorylation

■Paper Link: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32384