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Electroacupuncture regulates microglia polarization via lncRNA-mediated hippo pathway after ischemic stroke
Shenxu Chen1,2, Linmei Wang1, Ying Yuan1,3
1Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Microglia polarization and microglia-mediated inflammation play a crucial role in the development of ischaemic brain injury. Electroacupuncture (EA) has the function of anti-inflammatory, which has been thoroughly validated and utilized to treat ischemic brain damage. The fundamental mechanism by which EA alleviates ischemic brain damage by decreasing microglia polarization and microglia-mediated inflammation, however, remains unknown. In the current study, the activation of microglia and inflammatory cytokines was analyzed to confirm the anti-inflammatory function of EA in middle cerebral artery occlusion (MCAO) rats. Whole-transcriptome sequencing was used to examine the differentially expressed lncRNAs in the control, MCAO, and MCAO +EA groups. Our findings demonstrated that EA treatment reduced microglia activation and inflammatory cytokine production. In addition, there are 44 lncRNAs were found significantly different in three groups, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the predicted targets of these lncRNAs suggested that the Hippo pathway may contribute to the development of ischaemic brain injury and to the anti-inflammatory function of EA. Moreover, our data showed that lncRNA TCONS_00022826 (Lnc826) was upregulated in MCAO group, whereas blocked by EA treatment. Furthermore, in vitro OGD cell model data showed that Lnc826 promoted M1 polarization of microglia by regulating the Hippo pathway. Our data suggested that regulating microglia polarization via Lnc826-mediated hippo pathway is a possible mechanism of the EA treatment on ischemic brain injury.
Insights
Electroacupuncture (EA) reduces brain inflammation after ischemic stroke by regulating microglia polarization. This study identifies Lnc826 and the Hippo pathway as key targets for EA
Area of Science:
- Neuroscience
- Inflammation Research
- Traditional Chinese Medicine
Background:
- Microglia polarization and inflammation are critical in ischemic brain injury.
- Electroacupuncture (EA) is a validated anti-inflammatory treatment for ischemic stroke.
- The precise mechanism of EA's anti-inflammatory effect in ischemic brain injury is unclear.
Purpose of the Study:
- To investigate the anti-inflammatory mechanism of EA in a rat model of ischemic brain injury.
- To identify key molecular pathways and long non-coding RNAs (lncRNAs) involved in EA's therapeutic effects.
Main Methods:
- Middle cerebral artery occlusion (MCAA) rat model and in vitro oxygen-glucose deprivation (OGD) model.
- Analysis of microglia activation and inflammatory cytokines.
- Whole-transcriptome sequencing to identify differentially expressed lncRNAs.
- Bioinformatic analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Validation of specific lncRNA (TCONS_00022826/Lnc826) function in microglia polarization.
Main Results:
- EA treatment significantly reduced microglia activation and inflammatory cytokine levels in MCAO rats.
- Whole-transcriptome sequencing identified 44 differentially expressed lncRNAs, implicating the Hippo pathway.
- LncRNA Lnc826 was upregulated in MCAO and downregulated by EA, promoting M1 microglia polarization via the Hippo pathway.
Conclusions:
- EA exerts anti-inflammatory effects in ischemic brain injury by modulating microglia polarization.
- The Lnc826-mediated Hippo pathway is a potential molecular mechanism underlying EA's therapeutic action.
- Targeting Lnc826 and the Hippo pathway offers a novel therapeutic strategy for ischemic stroke.
