scholarly journals Regulatory Mechanisms of Injury and Repair after Hepatic Ischemia/Reperfusion

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Alex B. Lentsch

Hepatic ischemia/reperfusion injury is an important complication of liver surgery and transplantation. The mechanisms of this injury as well as the subsequent reparative and regenerative processes have been the subject of thorough study. In this paper, we discuss the complex and coordinated responses leading to parenchymal damage after liver ischemia/reperfusion as well as the manner in which the liver clears damaged cells and regenerates functional mass.

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Chrysanthos D. Christou ◽  
Georgios Tsoulfas

Introduction: Ischemia-reperfusion (I/R) injuries are caused by complex interrelated mechanisms and pathways. Regarding the liver, I/R injuries and their clinical manifestations are crucial for the surgical outcome. Despite its importance, there is no broadly accepted therapy either for the prevention or for the management of I/R injury. I/R injury of the liver can occur either during hepatic surgery (warm) or during the transplantation procedure (cold). MicroRNAs play a pivotal role in the mechanism of I/R injury, as they regulate the expression of the cellular participants and humoral factors associated with I/R injury. Objective: In this review, we highlight the microRNAs that are involved in the I/R injury of the liver, and the molecular pathways that they regulate. In addition, we discuss the potential role of circulating microRNAs as biomarkers and their role as pharmacological targets in the prevention, diagnosis and treatment of I/R injuries. Method: We conducted a comprehensive review of the PubMed bibliographic database regarding microRNAs and I/R injuries of the liver. Results: In diagnostics, microRNA panels could replace invasive diagnostic procedures, relieving patients of the associated complications. In therapeutics, microRNA agomirs, antagomirs and other drugs can be used to shift the balance between proapoptotic and survival pathways, to alleviate the liver damage caused by I/R. In transplantation procedures, microRNA profiling could decrease the incidence of early graft dysfunction, especially regarding marginal grafts. Conclusion: Although microRNAs seem a very promising clinical tool in the management of I/R injuries, further research is required, until microRNAs become a novel tool in the diagnosis and monitoring of an I/R injury of the liver.


2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ying Dong Du ◽  
Wen Yuan Guo ◽  
Cong Hui Han ◽  
Ying Wang ◽  
Xiao Song Chen ◽  
...  

AbstractDespite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.


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