Recently, Academician Li Xiaokun's team from the Oujiang Laboratory published a paper titled " FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice” in Nature Communications online " in the journal Nature Communications. The study found that FGF18 significantly alleviates hepatic ischemia-reperfusion injury and thus plays a key role in this process. Mechanistically, FGF18 protects against hepatic IRI mainly by reducing expression of USP16 and subsequently increasing ubiquitination of KEAP1, and thereby activating Nrf2 signaling. Moreover, the authors revealed that the regulation of USP16 by FGF18 occurs through a feedback loop involving USP16 and Nrf2, thus targeting the FGF18/USP16/KEAP1 regulatory axis represents a new clinical strategy to alleviate hepatic IRI and related pathological processes. Academician Li Xiaokun and Researcher Cong Weitao of Oujiang Laboratory, Professor Shen Jingling of Wenzhou University are the corresponding authors of this article. Tong Gaozan, a doctoral student at the School of Pharmaceutical Sciences of Wenzhou Medical University, Director Chen Yiming of the Department of Hepatic-Biliary-Pancreatic Surgery of the Second Affiliated Hospital of Wenzhou Medical University and Chen Xixi of the Pharmacy Department of Taizhou Central Hospital are the co-first authors.

Hepatic ischemia-reperfusion injury (IRI) is a common complication occurs during hepatic resection and transplantation, seriously affecting the prognosis of patients. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Fibroblast growth factor 18 (FGF18), a member of the exocrine fibroblast growth factor (FGF) family, widely participates in cellular metabolism. However, the role and mechanism of FGF18 in response to hepatic IRI has not been fully elucidated. In this study, a series of in vitro and in vivo experiments were conducted to explore the role of FGF18 in hepatic IRI and its specific regulatory mechanism.

Figure 1 The regulatory mechanism of FGF18 in hepatic IRI

The results of this study show that FGF18 significantly alleviates hepatic ischemia-reperfusion injury and thus plays a key role in this process, mainly by reducing oxidative stress and inflammation, thus ultimately decreasing apoptosis of hepatocytes. Experiments found that HSC-secreted FGF18 acts on and protects hepatocytes upon liver IRI. Mechanistically, FGF18 protects against hepatic IRI mainly by reducing the expression of USP16 and subsequently increasing ubiquitination of KEAP1, and thereby activating Nrf2 signaling. Moreover, the regulation of USP16 by FGF18 occurs through a feedback loop involving Nrf2 and USP16, thus targeting the FGF18/USP16/KEAP1 regulatory axis represents a new strategy to alleviate hepatic IRI and related pathological processes.

Source: https://www.nature.com/articles/s41467-023-41800-x

Written by: Tong Gaozan

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