Related Experiment Video
Updated: Jul 7, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
YTHDF2 alleviates microglia activation via promoting circHIPK2 degradation
Rongrong Huang1, Ming Sun2, Weiwei Wang3
1Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong 226001, China.
Abstract:
Microglial activation is a common cellular dysfunction in central nervous system inflammation, accompanied by abnormal expression of circular RNAs (circRNAs). YTHDF2, a N6-methyladenosine (m6A) reader, is known as a key element in RNA degradation. Here, lipolysaccharide induced microglia activation in mouse cortex and BV2 cells, accompanied by the decreased YTHDF2 and elevated circHIPK2. YTHDF2 overexpression or circHIPK2 knockdown in BV2 microglia inhibited the expressions of iNOS protein, IL-1β mRNA and IL-6 mRNA. Subsequent experiments revealed that YTHDF2 facilitated circHIPK2 degradation, thereby alleviating microglia activation. These findings suggest that YTHDF2 overexpression could serve as a therapeutic approach for inhibiting microglia activation.
Insights
Overexpressing YTHDF2, an m6A reader, reduces circular HIPK2 (circHIPK2) levels, inhibiting microglia activation and central nervous system inflammation.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Microglial activation is a hallmark of central nervous system inflammation, often involving dysregulated circular RNA (circRNA) expression.
- YTH domain-containing protein 2 (YTHDF2) is an N6-methyladenosine (m6A) reader crucial for RNA degradation.
Purpose of the Study:
- To investigate the role of YTHDF2 and circHIPK2 in lipopolysaccharide (LPS)-induced microglia activation.
- To explore the potential of targeting YTHDF2 for therapeutic intervention in neuroinflammation.
Main Methods:
- Induced microglia activation using lipopolysaccharide (LPS) in mouse cortex and BV2 cell models.
- Assessed the expression levels of YTHDF2 and circHIPK2.
- Manipulated YTHDF2 and circHIPK2 expression to evaluate their impact on inflammatory markers.
Main Results:
- LPS-induced microglia activation was associated with decreased YTHDF2 and increased circHIPK2 expression.
- YTHDF2 overexpression or circHIPK2 knockdown significantly inhibited the expression of iNOS, IL-1β, and IL-6.
- YTHDF2 was found to promote the degradation of circHIPK2, thereby mitigating microglia activation.
Conclusions:
- YTHDF2 plays a protective role by degrading circHIPK2, thus suppressing microglia activation.
- YTHDF2 overexpression presents a potential therapeutic strategy for managing neuroinflammation.
More Related Videos
10:40Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain
Published on: October 27, 2019
07:41Author Spotlight: Advancing Understanding Through Technological Innovations in Psychoneuroimmunology
Published on: May 31, 2024
