Mild hypothermia pretreatment protects hepatocytes against ischemia reperfusion injury via down-regulating miR-122 and IGF-1R/AKT pathway

Xiao, Qin; Ye, Qi Fa; Wang, Wei; Fu, Bi Qi; Xia, Zhi; Liu, Zhong Zhong; Zhang, Xing Jian; Wang, Yan Feng

doi:10.1016/j.cryobiol.2017.01.005

Cited by 20 publications

(8 citation statements)

References 34 publications

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“…The protective effect of low temperature pre-treatment on liver ischemia-reperfusion injury can be attenuated. The results of this study are also supported by research results of other studies [33,34].…”

Section: Animal Studysupporting

confidence: 90%

Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT

Xue

Wang

Su³

2020

Med Sci Monit

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Departmental sources Background: Ischemia-reperfusion injury is caused by a blood reperfusion injury in ischemic brain tissue, and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. MiR-122 is closely related to ischemia-reperfusion injury in the myocardium, kidney, and liver; however, the role in cerebral ischemiareperfusion injury has not been established. Material/Methods: In this study, cerebral ischemia-reperfusion injury was established in a rat model, and the control group was a sham-operated group. After ischemia-reperfusion injury for 6, 12, and 24 hours, brain tissue specimens were collected and the expression of miR-122 and DJ-1 were determined using quantitative real-time polymerase chain reaction. Flow cytometry was used to determine the reactive oxygen species (ROS) content. The modified Neurological Severity Score (mNSS) scale was used to evaluate the sensory and motor function defects of the rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme activity were determined. The rats in the cerebral ischemia-reperfusion injury model were divided into 2 groups (antagomir-NC group and antagomir miR-122 group). Brain neuron RN-c cells were divided into the following 4 groups: antagomir-NC, antagomir miR-122, pIRES2-blank, and pIRES2-DJ-1. Seventy-two hours after transfection, ischemia-reperfusion treatment was carried out and conventional cultured RN-c cells were used as the control group. Flow cytometry was used to detect apoptosis and western blot was used to detect the expression of DJ-1, PTEN, AKT, and p-AKT. Results: The expression of miR-122 increased significantly in the process of ischemia-reperfusion damage after cerebral infarction, while the expression of DJ-1 decreased significantly. Downregulation of miR-122 significantly increased the expression of DJ-1, enhanced the activity of the PTEN/PI3K/AKT pathway, reduced cell apoptosis, and alleviated cerebral ischemia-reperfusion injury. Conclusions: Inhibition of miR-122 can decrease cerebral ischemia-reperfusion injury by upregulating DJ-1-PTEN/PI3K/AKT pathway.

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Section: Animal Studysupporting

confidence: 90%

Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT

Xue

Wang

Su³

2020

Med Sci Monit

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“…To form an active enzyme, caspase need cleavage adjacent to aspartates to the liberation of a large and a small subunit forming α 2 β 2 tetramer[ 40 ]. The incidence has been reported the expression of caspase family, not only cleavage of caspase-3 and 9 [ 41 , 42 ], but also expression of caspase-3 and 9 [ 43 , 44 ] can be activated by ischemia/reperfusion. We showed that the expression of caspase-3 and cleavage of caspase-3 were enhanced in steatotic primary hepatocyte suffered HR.…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice

Li¹,

Takahara²,

Fujino³

et al. 2017

PLoS ONE

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Steatosis has a low tolerance against ischemia-reperfusion injury (IRI). To prevent IRI in the steatotic liver, we attempted to elucidate the protective effect of astaxanthin (ASTX) in the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet. Levels of lipid peroxidation and apoptosis, the expression of inflammatory cytokines and heme oxygenase (HO)-1, in the liver were assessed. Reactive oxygen species (ROS), inflammatory cytokines, apoptosis-related proteins and members of the signaling pathway were also examined in isolated Kupffer cells and/or hepatocytes from the steatotic liver. ASTX decreased serum ALT and AST levels, the amount of TUNEL, F4/80, or 4HNE-positive cells and the mRNA levels of inflammatory cytokines in MCDHF mice by IRI. Moreover, HO-1 and HIF-1α, phosphorylation of Akt and mTOR expressions were increased by ASTX. The inflammatory cytokines produced by Kupffer, which were subjected to hypoxia and reoxygenation (HR), were inhibited by ASTX. Expressions of Bcl-2, HO-1 and Nrf2 in hepatocytes by HR were increased, whereas Caspases activation, Bax and phosphorylation of ERK, MAPK, and JNK were suppressed by ASTX. Pretreatment with ASTX has a protective effect and is a safe therapeutic treatment for IRI, including for liver transplantation of the steatotic liver.

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“…Recently, the mechanisms of miR-122 in liver IRI have been determined. Xiao et al [ 78 ] found that miR-122 was increased in an anoxia-reoxygenation injury model in L02 cells. They identified that mild hypothermia pretreatment could induce a significant downregulation in miR-122 expression and reduce the hepatocellular injury, and these effects was abrogated by the miR-122 mimic.…”

Section: Mirnas and Liver Irimentioning

confidence: 99%

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

Yang

Chen

Meng

et al. 2018

IJMS

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Liver ischemia-reperfusion injury (IRI) is a major complication of hemorrhagic shock, liver transplantation, and other liver surgeries. It is one of the leading causes for post-surgery hepatic dysfunction, always leading to morbidity and mortality. Several strategies, such as low-temperature reperfusion and ischemic preconditioning, are useful for ameliorating liver IRI in animal models. However, these methods are difficult to perform in clinical surgeries. It has been reported that the activation of peroxisome proliferator activated receptor gamma (PPARγ) protects the liver against IRI, but with unidentified direct target gene(s) and unclear mechanism(s). Recently, FAM3A, a direct target gene of PPARγ, had been shown to mediate PPARγ’s protective effects in liver IRI. Moreover, noncoding RNAs, including LncRNAs and miRNAs, had also been reported to play important roles in the process of hepatic IRI. This review briefly discussed the roles and mechanisms of several classes of important molecules, including PPARγ, FAM3A, miRNAs, and LncRNAs, in liver IRI. In particular, oral administration of PPARγ agonists before liver surgery or liver transplantation to activate hepatic FAM3A pathways holds great promise for attenuating human liver IRI.

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Mild hypothermia pretreatment protects hepatocytes against ischemia reperfusion injury via down-regulating miR-122 and IGF-1R/AKT pathway

Cited by 20 publications

References 34 publications

Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT

Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT

Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

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