scholarly journals Protective mechanisms of telmisartan against hepatic ischemia/reperfusion injury in rats may involve PPARγ-induced TLR4/NF-κB suppression

2022 ◽  
Vol 145 ◽  
pp. 112374
Author(s):  
Mohamed A. Morsy ◽  
Seham A. Abdel-Gaber ◽  
Rehab A. Rifaai ◽  
Mostafa M. Mohammed ◽  
Anroop B. Nair ◽  
...  
2021 ◽  
Vol 8 ◽  
Author(s):  
Xinyao Tian ◽  
Yan Hu ◽  
Yuanxing Liu ◽  
Zhe Yang ◽  
Haiyang Xie ◽  
...  

Ischemic preconditioning (IPC) represents an effective intervention to relieve hepatic ischemia-reperfusion injury (IRI). Systematic detection of circRNA expression revealing the protection effect of IPC still remains to be elucidated. Here, we applied a microarray to detect circRNA and mRNA expression in ischemic liver with and without IPC (n = 3 in each group). Compared with the sham group, there were 39 circRNAs and 432 mRNAs increased and 38 circRNAs and 254 mRNAs decreased (fold change ≥1.5, P < 0.05) in the group of hepatic IRI. As the result of IPC intervention, 43 circRNAs and 64 mRNAs were increased, and 7 circRNAs and 31 mRNAs were decreased in the IPC group when compared with IRI. We then identified circRNA_017753 as the most possible target that may closely relate to IPC protective signaling and predicted Jade1 as the target related to circRNA_017753. Three possible circRNA–miRNA–mRNA axes were constructed that may play a vital role in protective mechanisms in IPC. The study for the first time systematically detects the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous novel clues to understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.


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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