Gastrodin combined with rhynchophylline inhibits cerebral ischaemia-induced inflammasome activation via upregulating miR-21–5p and miR-331–5p

Zhang, Hengsheng; Liu, Meifang; Ji, Xiong-Ying; Jiang, Chang-Rong; Li, Zili; Ouyang, Bo

doi:10.1016/j.lfs.2019.116935

Cited by 46 publications

(26 citation statements)

References 29 publications

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“…For example, TXNIP mediates the protective roles of miR-17 in in rats and PC12 cells after hypoxic-ischemic injury16. TXNIP is identified to function as the direct target of miR-21-5p, which participates the inhibitory effect of gastrodin combined with rhynchophylline in cerebral ischaemia-induced inflammasome activation [ 41 ]. These studies suggest that miRNAs may participate in the development of ischemic stroke by interacting with TXNIP.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Yang

et al. 2021

Exp Neurobiol

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Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3'-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Yang

et al. 2021

Exp Neurobiol

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“…The role of miR-21-5p in the brain, spinal cord, and heart injury has been widely reported (37)(38)(39). In one study, a combination of gastrodin and rhynchophylline inhibited the activation of inflammasomes induced by cerebral ischemia via upregulating the expression of miR-21-5p and miR-331-5p (40). In a related study, miR-21-5p modulated apoptosis of neurons after SCI via the miR-21-5p/PDCD4/caspase-3 pathway (34).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane pretreatment regulates abnormal expression of MicroRNAs associated with spinal cord ischemia/reperfusion injury in rats

Wang¹,

Fang²,

Wang³

et al. 2021

Ann Transl Med

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Background: Spinal cord ischemia/reperfusion injury (SCII) is one of the most serious spinal cord complications that stem from varied spine injuries or thoracoabdominal aortic surgery. Nevertheless, the molecular mechanisms underlying the SCII remain unclear.Methods: Male Sprague-Dawley (SD) rats were randomly divided into 5 groups of sham, SCII 24 h, SCII 72 h, sevoflurane preconditioning SCII 24 h (SCII 24 h+sevo), and sevoflurane preconditioning SCII 72 h (SCII 72 h+sevo) group. We then analyzed the expression of differentially expressed micro RNAs (DEmiRNAs) in these groups and their target genes. Functional enrichment analysis of their target genes was further performed using Metascape software. The microRNA-messenger RNA-pathway (miRNA-mRNA-pathway) network and the sevoflurane-miRNA-mRNA-pathway integrative network were further constructed to explore the molecular mechanisms underlying SCII and neuroprotective effects of sevoflurane against SCII. Molecular docking was also performed to evaluate the interactions between hub targets and sevoflurane. Finally, the expression levels of miR-21-5p and its target genes [mitogen-activated protein kinase kinase 3 and protein phosphatase 1 regulatory subunit 3B (MAP2K3 and PPP1R3B)] were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses.Results: We found that sevoflurane alters several miRNA expression following SCII at 24 and 72 h after reperfusion. It was shown that miR-221-3p, miR-181a-1-3p, and miR-21-5p were upregulated both at 24 and 72 h in the sevoflurane pre-treatment reperfusion groups. Functional enrichment analysis revealed that target genes for the above co-DEmiRNAs at 24 and 72 h in the SCII group with sevoflurane pretreatment participated in the mitogen-activated protein kinase (MAPK), ErbB, apoptosis, and transforming growth factor-beta (TGF-beta) signaling pathways. Both MAP2K3 and PPP1R3B were found to be common targets for sevoflurane and miRNA-mRNA-pathway (rno-miR-21-5p). It was shown that MAP2K3 regulates the MAPK signaling and the T cell receptor signaling pathways, whereas PPP1R3B regulates the ErbB signaling pathway. Molecular docking further revealed that sevoflurane strongly binds the MAP2K3 and PPP1R3B proteins. Compared to the sham group, SCII induced significant under-expression of miR-21-5p but upregulated PPP1R3B and MAP2K3 proteins; sevoflurane pretreatment increased the expression of miR-21-5p but decreased those of PPP1R3B and MAP2K3 proteins. Conclusions:In general, sevoflurane regulates the expression of several miRNAs following SCII. In particular, sevoflurane might protect against SCII via regulating the expression of miR-21-5p, its target genes (MAP2K3 and PPP1R3B), and related signaling pathways.

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“…When TXNIP and NLRP3 are decreased, tissue damage associated with cerebral ischemia is reduced [219,220]. Many other original compounds with antioxidant properties are able to decrease the expression of TXNIP and attenuate brain damage and neurotoxicity following ischemia by suppressing the activation of the inflammasome [103,127,221,222]. Nrf2 is reported to inhibit the NLRP3 inflammasome by regulating the TRX/TXNIP complex and consequently hampers cerebral ischemia reperfusion injury [102].…”

Section: Txnip As a Marker In Cerebral Ischemiamentioning

confidence: 99%

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

Domingues

Jolibois

Rougé

et al. 2021

IJMS

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Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

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Gastrodin combined with rhynchophylline inhibits cerebral ischaemia-induced inflammasome activation via upregulating miR-21–5p and miR-331–5p

Cited by 46 publications

References 29 publications

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Sevoflurane pretreatment regulates abnormal expression of MicroRNAs associated with spinal cord ischemia/reperfusion injury in rats

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

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