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Microglial lnc-U90926 facilitates neutrophil infiltration in ischemic stroke via MDH2/CXCL2 axis
- Source :
- Mol Ther
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Dysregulated long non-coding RNAs (lncRNAs) have been shown to contribute to the pathogenesis of ischemic stroke. However, the potential role of lncRNAs in post-stroke microglial activation remains largely unknown. Here, we uncovered that lncRNA-U90926 was significantly increased in microglia exposed to ischemia/reperfusion both in vivo and in vitro. In addition, adenovirus-associated virus (AAV)-mediated microglial U90926 silencing alleviated neurological deficits and reduced infarct volume in experimental stroke mice. Microglial U90926 knockdown could reduce the infiltration of neutrophils into ischemic lesion site, which might be attributed to the downregulation of C-X-C motif ligand 2 (CXCL2). Mechanistically, U90926 directly bound to malate dehydrogenase 2 (MDH2) and competitively inhibited the binding of MDH2 to the CXCL2 3' untranslated region (UTR), thus protecting against MDH2-mediated decay of CXCL2 mRNA. Taken together, our study demonstrated that microglial U90926 aggravated ischemic brain injury via facilitating neutrophil infiltration, suggesting that U90926 might be a potential biomarker and therapeutic target for ischemic stroke.
- Subjects :
- Male
Chemokine CXCL2
Primary Cell Culture
Ischemia
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Malate Dehydrogenase
Drug Discovery
Genetics
medicine
Animals
Humans
Gene silencing
Molecular Biology
Stroke
Cells, Cultured
Ischemic Stroke
030304 developmental biology
Pharmacology
0303 health sciences
Gene knockdown
Microglia
business.industry
medicine.disease
Up-Regulation
Mice, Inbred C57BL
Disease Models, Animal
CXCL2
HEK293 Cells
medicine.anatomical_structure
Neutrophil Infiltration
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Original Article
RNA, Long Noncoding
5' Untranslated Regions
business
Infiltration (medical)
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....f21dbd9561d6c15a1ff40ddfb5829457