MiR-30a Positively Regulates the Inflammatory Response of Microglia in Experimental Autoimmune Encephalomyelitis
Xue Fang1, Dingya Sun1, Zhihong Wang1
1Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Institute of Neuroscience, Second Military Medical University, Shanghai, 200433, China.
Abstract:
Multiple sclerosis (MS) is a classical inflammatory demyelinating disease of the central nervous system (CNS). Microglia are the main resident immune cells in the CNS and are closely associated with the pathogenesis of MS. In the present study, we found that miR-30a was highly expressed in jellyfish-like microglia in chronic active lesions of MS patients, as well as in the microglia of mice with experimental autoimmune encephalomyelitis (EAE) at the chronic phase. In vitro, the conditioned supernatant of mouse microglia overexpressing miR-30a promoted the apoptosis of oligodendrocyte precursor cells (OPCs), and inhibited OPC differentiation. In vivo, overexpressing miR-30a in transplanted microglia exacerbated the progression of EAE. Overexpression and knock-down experiments in primary cultured mouse microglia showed that miR-30a increased the expression of IL-1β and iNOS, which are pro-inflammatory, while inhibiting the expression of Ym-1 and CD206. Mechanistically, miR-30a inhibited the expression of Ppargc1b, which is the co-activator of peroxisome proliferator-activated receptor gamma, resulting in pro-inflammatory effects. Our work shows that miR-30a is an important regulator of the inflammatory response in microglia, and may be a promising therapeutic target for inflammatory diseases like MS in the CNS.
Insights
MicroRNA-30a (miR-30a) promotes inflammation and damage in multiple sclerosis (MS) by affecting microglia and oligodendrocyte precursor cells. Targeting miR-30a may offer a new therapeutic strategy for CNS inflammatory diseases.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a central nervous system (CNS) inflammatory demyelinating disease.
- Microglia, the resident immune cells of the CNS, play a critical role in MS pathogenesis.
Purpose of the Study:
- Investigate the role of microRNA-30a (miR-30a) in microglia-mediated inflammation in MS.
- Determine miR-30a's potential as a therapeutic target for CNS inflammatory diseases.
Main Methods:
- Analysis of miR-30a expression in MS lesions and experimental autoimmune encephalomyelitis (EAE) mouse models.
- In vitro studies using primary microglia and oligodendrocyte precursor cells (OPCs).
- In vivo experiments involving microglia transplantation in EAE mice.
Main Results:
- miR-30a was highly expressed in microglia from MS patients and EAE mice.
- Overexpression of miR-30a in microglia promoted OPC apoptosis, inhibited differentiation, and exacerbated EAE.
- miR-30a upregulated pro-inflammatory markers (IL-1β, iNOS) and downregulated anti-inflammatory markers (Ym-1, CD206) in microglia.
- miR-30a inhibited Ppargc1b expression, leading to pro-inflammatory effects.
Conclusions:
- miR-30a acts as a key regulator of microglial inflammatory responses in the CNS.
- miR-30a is implicated in the pathogenesis of multiple sclerosis.
- miR-30a represents a potential therapeutic target for MS and other CNS inflammatory conditions.
