Inhibition of microRNA-128-3p alleviates liver ischaemia–reperfusion injury in mice through repressing the Rnd3/NF‐<b>κ</b>B axis

Mou, Tong; Luo, Yunhai; Huang, Zuotian; Zheng, Daofeng; Pu, Xingyu; Shen, Ai; Pu, Jing; Li, Tingting; Dai, Jiangwen; Chen, Wei; Wu, Zhongjun

doi:10.1177/1753425920928449

Cited by 20 publications

(19 citation statements)

References 39 publications

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“…Of note, the activation of p65 is essential for the development of DOX-mediated cardiotoxicity, and inhibition of p65 could attenuate DOX-induced cardiotoxicity [ 25 , 26 ]. A previous study found that repression of miR-128-3p could alleviate liver injury through the regulation of p65 [ 27 ]. Here, we also found that repression of miR-128-3p reduced p65 activity and expression, and decreased myocardial inflammation levels in DOX-treated hearts.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ

Zhang

Yang

2021

PPAR Research

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Background. The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was involved into the regulation of redox balance. However, the role of miR-128-3p in DOX-related cardiac injury remains not yet understood. The aim of this study was to investigate the biological effect of miR-128-3p in DOX-induced cardiotoxicity. Methods. To induce DOX-related acute cardiac injury, mice were subjected to a single injection of DOX. Inhibition of myocardial miR-128-3p was achieved by an adeno-associated virus (AAV9) system carrying a miR-128-3p sponge. Results. The data in our study indicated that miR-128-3p was upregulated in DOX-treated hearts and cardiomyocytes. Inhibition of miR-128-3p attenuated DOX-related cardiac injury and improved cardiac function in mice. Moreover, miR-128-3p inhibition could suppress myocardial inflammatory response, oxidative damage, and cell apoptotic death in DOX-treated mice. Further analysis showed that miR-128-3p could directly target peroxisome proliferator-activated receptor γ (PPAR-γ) and decrease PPAR-γ expression. Moreover, the protective effects provided by miR-128-3p inhibition were abolished by a PPAR-γ antagonist in vivo and in vitro. Conclusions. miR-128-3p inhibition attenuated DOX-related acute cardiac injury via the regulation of PPAR-γ in mice.

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Section: Discussionmentioning

confidence: 99%

Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ

Zhang

Yang

2021

PPAR Research

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“…For example, Shen et al found that miR-24-3p protected against hepatic I/R injury in mice through the repression of STING signaling pathway (Shen et al, 2020). Mou et al reported that miR-128-3p inhibition could alleviate liver I/R injury through suppressing Rnd3/NF-κB axis in mice (Mou et al, 2020). Zhang et al demonstrated that miR-449b-5p attenuated hepatic I/R injury by targeting HMGB1 (Zhang et al, 2019a).…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Postconditioning Attenuates Hepatic Ischemia-Reperfusion Injury by Limiting HMGB1/TLR4/NF-κB Pathway via Modulating microRNA-142 in vivo and in vitro

et al. 2021

Front. Pharmacol.

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Preconditioning of sevoflurane (Sevo) has been demonstrated to protect the liver from ischemia/reperfusion (I/R) injury. However, it is unknown whether it has hepatoprotective when given at the onset of reperfusion (postconditioning), a protocol with more clinical impact. The present study aimed to explore the hepatoprotective effects of Sevo postconditioning against hepatic IR injury in vivo and in vitro and the possible mechanisms. Using a mouse model of hepatic I/R, Sevo postconditioning significantly improved hepatic injury after reperfusion, as demonstrated by reduced AST, ALT, and LDH serum levels and reduced histologic damage in liver tissues. Furthermore, Sevo postconditioning could suppress the apoptosis, inhibit oxidative stress and inflammatory response in liver tissue of HIRI mice, as well as improve the survival rate of HIRI mice. Through analyzing GSE72314 from the gene expression omnibus (GEO) database, it was demonstrated that microRNA (miR)-142 is downregulated by HIRI, which was reversed by Sevo treatment. Further investigation showed that agomiR-142 injection could enhance the hepatoprotective effects of Sevo postconditioning on I/R injury, while antagomiR-142 reversed these effects in mice. Notably, high mobility group box 1 (HMGB1), an important inflammatory factor, was directly targeted by miR-142 in hepatic cells, and we further found that Sevo could inhibit the expression of HMGB1 through up-regulating miR-142 expression in HIRI mice model. In addition, we found that I/R injury induced the activation of TLR4/NF-κB inflammatory pathway was partially suppressed by Sevo postconditioning, and miR-142 mediated the regulatory role of Sevo postconditioning. In line with the in vivo results, Sevo treatment improved the cell viability, inhibited cell apoptosis, oxidative stress and inflammatory response in vitro HIRI model, while these effects were reversed by antagomiR-142 transfection. Collectively, our findings demonstrated that Sevo postconditioning counteracts the downregulation of miR-142 provoked by I/R, in turn decreased the expression of HMGB1, blocking TLR4/NF-κB pathway activation, thus improving hepatic I/R injury. Our data suggest that Sevo may be a valuable alternative anaesthetic agent in liver transplantation and major liver surgeries.

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“…For example, Li et al established that miR-142-3p was downregulated in the liver tissues after I/R, while upregulated miR-142-3p ameliorated liver injury by targeting myristoylated alanine-rich C-kinase substrate (MARCKS) ( 7 ). Other miRNAs, such as miR-125b, miR-128-3b and miR-450b-5p ( 5 , 6 , 8 ), are reportedly involved in liver I/R. miR-140-5p has been investigated extensively in tumor research, including glioma, breast and lung cancer, and hepatocellular carcinoma ( 13 , 14 , 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs or miRs) are a class of highly conserved, endogenous, small non-coding RNAs that play important regulatory roles in a variety of biological processes and usually inhibit the expression of target genes by binding to the 3'-untranslated regions (3'-UTRs) of target mRNAs (4). In liver I/R injury, miRNAs, such as miR-125b, miR-128-3p, miR-142-3p, miR-450b-5p, and miR-27a, participate in the regulation of liver I/R injury through inflammatory responses, oxidative stress, apoptosis, autophagy, and energy metabolism (5)(6)(7)(8)(9). miR-140-5p, also known as miR-140, was first identified in zebrafish in 2005 (10).…”

Section: Introductionmentioning

confidence: 99%

miR‑140‑5p alleviates mouse liver ischemia/reperfusion injury by targeting CAPN1

Chen

Tang

et al. 2021

Mol Med Rep

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Ischemia/reperfusion (I/R)-induced liver injury remains a primary concern in liver transplantation and hepatectomy. Previous studies have indicated that microRNAs (miRs) are involved in multiple pathophysiological processes, including liver I/R. miR-140-5p reportedly inhibits inflammatory responses and apoptosis in several diseases; however, the role of miR-140-5p in liver I/R remains unknown. The present study aimed to investigate the potential role and mechanism of miR-140-5p on liver I/R injury. Mouse liver I/R and mouse AML12 cell hypoxia/reoxygenation (H/R) models were established. miR-140-5p mimics, inhibitor or agonists were used to overexpress or inhibit miR-140-5p in vitro and in vivo. Reverse transcription-quantitative polymerase chain reaction was used to detect miR-140-5p expression. Liver and cell injury were evaluated using several biochemical assays. The association between miR-140-5p and calpain-1 (CAPN1) was confirmed using a dual-luciferase reporter assay. The results revealed that miR-140-5p expression was decreased in the mouse model of liver I/R injury and AML12 cells subjected to H/R, while overexpressed miR-140-5p reduced liver injury in vivo and cell injury in vitro. In addition, CAPN1 was determined to be a target of miR-140-5p; overexpressed CAPN1 abrogated the effect of miR-140-5p on H/R-induced cell injury. The present study indicated that miR-140-5p protected against liver I/R by targeting CAPN1, which may provide a novel therapeutic target for liver I/R injury.

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Inhibition of microRNA-128-3p alleviates liver ischaemia–reperfusion injury in mice through repressing the Rnd3/NF‐κB axis

Cited by 20 publications

References 39 publications

Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ

Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ

Sevoflurane Postconditioning Attenuates Hepatic Ischemia-Reperfusion Injury by Limiting HMGB1/TLR4/NF-κB Pathway via Modulating microRNA-142 in vivo and in vitro

miR‑140‑5p alleviates mouse liver ischemia/reperfusion injury by targeting CAPN1

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