KLF2 up-regulates IRF4/HDAC7 to protect neonatal rats from hypoxic-ischemic brain damage

Wu, Fan; Li, Chunlin

doi:10.1038/s41420-022-00813-z

Cited by 13 publications

(10 citation statements)

References 31 publications

(39 reference statements)

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“…Over-expression of PGC-1α in neurons could inhibit the neuronal apoptosis, while inhibition of PGC-1α expression could induce the neuronal apoptosis (Yang et al, 2022b). It was found that the expression of PGC-1α and related antioxidant components were increased in AIS patients, and the increased level of PGC-1α was mainly located in activated astrocytes (Wu and Li, 2022;Wu et al, 2015). By over-expressing PGC-1α in astrocytes in vitro, ROS levels were reduced, pro-in ammatory factor release was reduced, and neuronal activity was ultimately improved.…”

Section: Discussionmentioning

confidence: 99%

“…As is known to all, the research of miR-126a-5p focuses on the eld of cancer treatment (Wu and Li, 2022), and the research on AIS and neuronal injury is still a blank. In order to further study the molecular mechanism of miR-126a-5p in AIS and neuronal injury, we rst analyzed the potential target circRNA binding by miR-126a-5p.…”

Section: Mir-126a-5p Is the Target Gene Of Circrna_0000927mentioning

confidence: 99%

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CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in acute ischemic stroke

Wang

Qian

et al. 2022

Preprint

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Purpose We investigated the role of CircRNA_0000927 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-126a-5p/PGC-1α axis to find a novel clinical drug target and prediction and treatment of AIS. Methods The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. CircRNA_0000927 localization was performed using fluorescence in situ hybridization (FISH). CircRNA_0000927, miR-126a-5p and PGC-1α mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PGC-1α protein expression was performed using Western blotting. IL-1β was detected by ELISA assay. Results Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of circRNA_0000927 to miR-126a-5p and miR-126a-5p to PGC-1α. CircRNA_0000927 and PGC-1α expression was significantly down-regulated and miR-126a-5p expression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β was significantly up-regulated in vivo and in vitro. The over-expression of circRNA_0000927 and miR-126a-5p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β and up-regulate the expression of PGC-1α in vitro. Finally, over-expression of circRNA_0000927 and miR-126a-5p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. Conclusion CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in AIS.

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Section: Discussionmentioning

confidence: 99%

Section: Mir-126a-5p Is the Target Gene Of Circrna_0000927mentioning

confidence: 99%

CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in acute ischemic stroke

Wang

Qian

et al. 2022

Preprint

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“…Second, the pathogenesis of neonatal HIE is complicated; we only focused on oxidative stress and apoptosis, and other pathological factors, such as inflammation, mitochondrial dysfunction and Frontiers in Pharmacology frontiersin.org excitotoxicity, might be involved. Finally, the expression of Nrf2 can be enhanced by the activation of silent information regulator 2-related enzyme 1 (SIRT1), ameliorating HIBD-induced ferroptosis and exerting a neuroprotective effect (Li C. et al, 2022). Whether EA can alleviate HIBD by inhibiting ferroptosis through the SIRT1/ Nrf2 signaling pathway needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, we also found obvious cerebral infarct areas in the HI group, which were then decreased by EA administration. Morphological changes in the ipsilateral brain are one of the major characteristics of neonatal HIE ( Wu and Li, 2022 ). In the present study, we observed morphological injuries in the ipsilateral parietal cortex and the hippocampal CA1 region by H&E staining, and the results showed that EA treatment attenuated HIBD-mediated neuronal atrophy and their disordered distribution.…”

Section: Discussionmentioning

confidence: 99%

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway

Chen²,

Dong³

et al. 2023

Front. Pharmacol.

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Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

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“…Frontiers in Aging Neuroscience 09 frontiersin.org (Wu and Li, 2022). Hdac7 was down-regulated in postoperative period.…”

Section: Functional Enrichment Analysis and Subclassificationmentioning

confidence: 93%

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction

Zhang

Suo

et al. 2023

Front. Aging Neurosci.

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Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs–miRNAs–mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.

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KLF2 up-regulates IRF4/HDAC7 to protect neonatal rats from hypoxic-ischemic brain damage

Cited by 13 publications

References 31 publications

CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in acute ischemic stroke

CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in acute ischemic stroke

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction

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