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Circular RNA circDNAJC5 Regulates Ultrafine Particle-Disrupted Microglial Lipid Metabolism via the Sphingolipid
Hui-Xian Zeng1, Guoliang Li2, Qing-Guo Zeng1
1Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Environment & Health (Washington, D.C.)
|July 22, 2026
Summary
Ultrafine particles disrupt brain microglial function by downregulating circDNAJC5, a key regulator of lipid metabolism. This epigenetic change links environmental exposure to Alzheimer
Area of Science:
- Neuroscience
- Environmental Health
- Epigenetics
Background:
- Ultrafine particles (PM0.1) penetrate the brain, disrupting microglial function.
- Dysregulated microglial lipid metabolism is implicated in Alzheimer's disease (AD).
- Epigenetic regulation by circular RNAs (circRNAs) in PM0.1-exposed microglia is poorly understood.
Purpose of the Study:
- Investigate the role of circRNAs in PM0.1-induced microglial lipid metabolism disruption.
- Identify specific circRNAs involved in this process.
- Elucidate the underlying epigenetic mechanisms linking environmental exposure to neuroinflammation and metabolic dysfunction.
Main Methods:
- Established in vitro models of PM0.1-treated microglia (HMC3 and BV2).
- Identified and quantified circRNA expression changes.
- Performed circRNA silencing and overexpression experiments.
- Investigated circRNA-miRNA-mRNA interactions (ceRNA network analysis).
- Validated findings in PM-exposed mice, AD mouse models, and human blood samples.
Main Results:
- Identified circDNAJC5 as significantly downregulated in PM0.1-exposed microglia.
- circDNAJC5 silencing aggravated lipid dysregulation; overexpression mitigated it.
- circDNAJC5 acts as a molecular sponge for miR-98-5p, regulating sphingomyelin synthase 1 (SMS1).
- Downregulated circDNAJC5 and lipid abnormalities were observed in vivo and in human samples.
Conclusions:
- circDNAJC5 plays a crucial role in regulating microglial lipid metabolism under PM0.1 exposure.
- This study reveals an epigenetic mechanism linking environmental pollution to neuroinflammation and AD pathogenesis.
- circDNAJC5 is a potential biomarker for neurodegenerative and metabolic disorders.
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