scholarly journals Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury

2022 ◽  
Vol 8 ◽  
Author(s):  
Xin-li Mao ◽  
Yue Cai ◽  
Ya-hong Chen ◽  
Yi Wang ◽  
Xiu-xiu Jiang ◽  
...  

Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects.

2006 ◽  
Vol 175 (4) ◽  
pp. i9-i9 ◽  
Author(s):  
Courtney M. Lappas ◽  
Yuan-Ji Day ◽  
Melissa A. Marshall ◽  
Victor H. Engelhard ◽  
Joel Linden

Hepatology ◽  
2007 ◽  
Vol 47 (1) ◽  
pp. 215-224 ◽  
Author(s):  
Satoshi Kuboki ◽  
Thomas Shin ◽  
Nadine Huber ◽  
Thorsten Eismann ◽  
Elizabeth Galloway ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Zenan Yuan ◽  
Linsen Ye ◽  
Xiao Feng ◽  
Tian Zhou ◽  
Yi Zhou ◽  
...  

Hepatic ischemia-reperfusion injury (IRI) is the most common cause of liver damage leading to surgical failures in hepatectomy and liver transplantation. Extensive inflammatory reactions and oxidative responses are reported to be the major processes exacerbating IRI. The involvement of Yes-associated protein (YAP) in either process has been suggested, but the role and mechanism of YAP in IRI remain unclear. In this study, we constructed hepatocyte-specific YAP knockout (YAP-HKO) mice and induced a hepatic IRI model. Surprisingly, the amount of serum EVs decreased in YAP-HKO compared to WT mice during hepatic IRI. Then, we found that the activation of YAP increased EV secretion through F-actin by increasing membrane formation, while inhibiting the fusion of multivesicular body (MVB) and lysosomes in hepatocytes. Further, to explore the essential elements of YAP-induced EVs, we applied mass spectrometry and noticed CD47 was among the top targets highly expressed on hepatocyte-derived EVs. Thus, we enriched CD47+ EVs by microbeads and applied the isolated CD47+ EVs on IRI mice. We found ameliorated IRI symptoms after CD47+ EV treatment in these mice, and CD47+ EVs bound to CD172α on the surface of dendritic cells (DCs), which inhibited DC activation and the cascade of inflammatory responses. Our data showed that CD47-enriched EVs were released in a YAP-dependent manner by hepatocytes, which could inhibit DC activation and contribute to the amelioration of hepatic IRI. CD47+ EVs could be a potential strategy for treating hepatic IRI.


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