FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion

Zhou, Hongzhi; Wang, Xin; Ma, Liming; Deng, Aiqing; Wang, Shouyan; Xia, Chen

doi:10.1080/00207454.2018.1564290

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…GLI2 played a significant role in the pathogenesis of cancer, and some studies implicated that GLI2 mediated regulation of cytokines in TME to promote cancer cell biology ( Elsawa et al, 2011 ; Han et al, 2017 ). FOXOs transcription factors play crucial roles in stress resistance, inflammation, metabolism, autophagy, apoptosis, and proliferation ( Zhou et al, 2019 ). The function of FOXO3 is highly regulated via posttranslational modifications, such as methylation, acetylation, and phosphorylation ( Hedrick et al, 2012 ; Tia et al, 2018 ; Wang, Hu & Liu, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…The function of FOXO3 is highly regulated via posttranslational modifications, such as methylation, acetylation, and phosphorylation ( Hedrick et al, 2012 ; Tia et al, 2018 ; Wang, Hu & Liu, 2017 ). Zhou et al suggested that the activation of FOXO3 could induce brain autophagy and contribute to brain damage after IRI ( Zhou et al, 2019 ). A recent study demonstrated that pyroptosis of cardiomyocytes in IRI was regulated by miR-149 via the directly targeting of FOXO3 ( Lin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats

Chen

Han

Wang

2021

PeerJ

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Spinal cord ischemia-reperfusion injury (SCII) is a pathological process with severe complications such as paraplegia and paralysis. Aberrant miRNA expression is involved in the development of SCII. Differences in the experimenters, filtering conditions, control selection, and sequencing platform may lead to different miRNA expression results. This study systematically analyzes the available SCII miRNA expression data to explore the key differently expressed miRNAs (DEmiRNAs) and the underlying molecular mechanism in SCII. A systematic bioinformatics analysis was performed on 23 representative rat SCII miRNA datasets from PubMed. The target genes of key DEmiRNAs were predicted on miRDB. The DAVID and TFactS databases were utilized for functional enrichment and transcription factor binding analyses. In this study, 19 key DEmiRNAs involved in SCII were identified, 9 of which were upregulated (miR-144-3p, miR-3568, miR-204, miR-30c, miR-34c-3p, miR-155-3p, miR-200b, miR-463, and miR-760-5p) and 10 downregulated (miR-28-5p, miR-21-5p, miR-702-3p, miR-291a-3p, miR-199a-3p, miR-352, miR-743b-3p, miR-125b-2-3p, miR-129-1-3p, and miR-136). KEGG enrichment analysis on the target genes of the upregulated DEmiRNAs revealed that the involved pathways were mainly the cGMP-PKG and cAMP signaling pathways. KEGG enrichment analysis on the target genes of the downregulated DEmiRNAs revealed that the involved pathways were mainly the Chemokine and MAPK signaling pathways. GO enrichment analysis indicated that the target genes of the upregulated DEmiRNAs were markedly enriched in biological processes such as brain development and the positive regulation of transcription from RNA polymerase II promoter. Target genes of the downregulated DEmiRNAs were mainly enriched in biological processes such as intracellular signal transduction and negative regulation of cell proliferation. According to the transcription factor analysis, the four transcription factors, including SP1, GLI1, GLI2, and FOXO3, had important regulatory effects on the target genes of the key DEmiRNAs. Among the upregulated DEmiRNAs, miR-3568 was especially interesting. While SCII causes severe neurological deficits of lower extremities, the anti-miRNA oligonucleotides (AMOs) of miR-3568 improve neurological function. Cleaved caspase-3 and Bax was markedly upregulated in SCII comparing to the sham group, and miR-3568 AMO reduced the upregulation. Bcl-2 expression levels showed a opposite trend as cleaved caspase-3. The expression of GATA6, GATA4, and RBPJ decreased after SCII and miR-3568 AMO attenuated this upregulation. In conclusion, 19 significant DEmiRNAs in the pathogenesis of SCII were identified, and the underlying molecular mechanisms were validated. The DEmiRNAs could serve as potential intervention targets for SCII. Moreover, inhibition of miR-3568 preserved hind limb function after SCII by reducing apoptosis, possibly through regulating GATA6, GATA4, and RBPJ in SCII.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats

Chen

Han

Wang

2021

PeerJ

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“…GLI2 played a significant role in the pathogenesis of cancer, and some studies implicated that GLI2 mediated regulation of cytokines in TME to promote cancer cell biology (Elsawa et al 2011;Han et al 2017). FOXOs transcription factors play crucial roles in stress resistance, inflammation, metabolism, autophagy, apoptosis, and proliferation (Zhou et al 2019). The function of FOXO3 is highly regulated via posttranslational modifications, such as methylation, acetylation, and phosphorylation (Hedrick et al 2012;Tia et al 2018;Wang et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats (v0.1)"

2021

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Spinal cord ischemia-reperfusion injury (SCII) is a pathological process with severe complications such as paraplegia and paralysis. Aberrant miRNA expression is involved in the development of SCII. Differences in the experimenters, filtering conditions, control selection, and sequencing platform may lead to different miRNA expression results. This study systematically analyzes the available SCII miRNA expression data to explore the key differently expressed miRNAs (DEmiRNAs) and the underlying molecular mechanism in SCII. A systematic bioinformatics analysis was performed on 23 representative rat SCII miRNA datasets from PubMed. The target genes of key DEmiRNAs were predicted on miRDB. The DAVID and TFactS databases were utilized for functional enrichment and transcription factor binding analyses. In this study, 19 key DEmiRNAs involved in SCII were identified, 9 of which were upregulated (miR-144-3p, miR-3568, miR-204, miR-30c, miR-34c-3p, miR-155-3p, miR-200b, miR-463, and miR-760-5p) and 10 downregulated (miR-28-5p, miR-21-5p, miR-702-3p, miR-291a-3p, miR-199a-3p, miR-352, miR-743b-3p, miR-125b-2-3p, miR-129-1-3p, and miR-136). KEGG enrichment analysis on the target genes of the upregulated DEmiRNAs revealed that the involved pathways were mainly cGMP-PKG and cAMP signaling pathway. KEGG enrichment analysis on the target genes of the downregulated DEmiRNAs revealed that the involved pathways were mainly Chemokine and MAPK signaling pathway. GO enrichment analysis indicated that the target genes of the upregulated DEmiRNAs were markedly enriched in biological processes such as brain development and the positive regulation of transcription from RNA polymerase II promoter. Target genes of the downregulated DEmiRNAs were mainly enriched in biological processes such as intracellular signal transduction and negative regulation of cell proliferation. According to the transcription factor analysis, the 4 transcription factors, including SP1, GLI1, GLI2, and FOXO3, had important regulatory effects on the target genes of the key DEmiRNAs. Among the upregulated DEmiRNAs, miR-3568 was especially interesting. While SCII causes severe neurological deficits of lower extremities, the anti-miRNA oligonucleotides (AMOs) of miR-3568 improve neurological function.

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“…VEGF signaling pathway is involved in angiogenesis after CIR (Sun et al, 2015;Ho et al, 2017). FoxO signaling pathway is involved in oxidative stress in CIR (Yoo et al, 2012;Zhou et al, 2019). HIF-1 signaling pathway is involved in the induction of hypoxia after CIR (Singh et al, 2012).…”

Section: Group 1 Day 3 Days 5 Days 7 Daysmentioning

confidence: 99%

Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

Yang

Zeng

et al. 2021

Front. Pharmacol.

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Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

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FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion

Cited by 20 publications

References 37 publications

Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats

Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats

Peer Review #1 of "Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats (v0.1)"

Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

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