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Updated: Oct 1, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
YY1 PROMOTES MICROGLIA M2 POLARIZATION THROUGH THE MIR-130A-3P/TREM-2 AXIS TO ALLEVIATE SEPSIS-ASSOCIATED
Liang-Shan Peng1, Yan Xu, Qiao-Sheng Wang
1The First Affiliated Hospital, Department of Critical Care Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Abstract:
Purpose: Sepsis-associated encephalopathy (SAE) induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation. Yin Yang 1 (YY1) is an important transcription factor that acts as a key role in sepsis and neuroepithelium development. However, the function of YY1 in SAE remains unclear. Our study aimed to probe the intrinsic and concrete molecular mechanism of YY1 in SAE. Methods: SAE cell model and SAE animal model were constructed by lipopolysaccharide (LPS) treatment and cecal ligation and puncture surgery, respectively. Behavioral tests were performed to analyze the cognitive function. The polarization state of mouse microglia (BV-2 cells) was assessed by flow cytometry assay. The mRNA and protein expressions were assessed by qRT-PCR and western blot. Finally, the binding relationships between YY1, miR-130a-3p, andTREM-2were verified by dual luciferase reporter gene assay and/or ChIP assay. Results: Here our results described that YY1 and TREM-2 were downregulated and miR-130a-3p was upregulated in SAE. YY1 overexpression could promote M2 polarization of microglia, and alleviate neuroinflammation and behavioral deficits in vitro and in vivo. YY1 could inhibit miR-130a-3p promoter activity. As expected, miR-130a-3p overexpression abolished the effects of YY1 overexpression on LPS-treated BV-2 cells. Besides, TREM-2 was identified as the target of miR-130a-3p. TREM-2 silencing could reverse the effects of miR-130a-3p inhibition on LPS-treated BV-2 cells. Conclusion: Taken together, YY1 promoted microglia M2 polarization via upregulating TREM-2 by interacting with miR-130a-3p promoter, suggesting YY1 overexpression might be a novel therapeutic strategy of SAE.
Insights
Yin Yang 1 (YY1) overexpression improves cognitive function in sepsis-associated encephalopathy (SAE) by promoting beneficial microglia (M2) polarization. This occurs through upregulating TREM-2 by interacting with miR-130a-3p, suggesting YY1 as a potential therapeutic target for SAE.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Sepsis-associated encephalopathy (SAE) causes cognitive dysfunction through neuroinflammation.
- Yin Yang 1 (YY1) is a transcription factor involved in sepsis and neurodevelopment, but its role in SAE is unknown.
Purpose of the Study:
- To investigate the molecular mechanism of YY1 in SAE.
- To determine if YY1 influences microglial polarization and cognitive function in SAE.
Main Methods:
- SAE models (cell and animal) were induced using lipopolysaccharide (LPS) and cecal ligation and puncture.
- Cognitive function was assessed via behavioral tests.
- Microglial polarization, gene/protein expression (qRT-PCR, Western blot), and molecular interactions (dual luciferase reporter, ChIP assays) were analyzed.
Main Results:
- YY1 and TREM-2 were downregulated, while miR-130a-3p was upregulated in SAE.
- YY1 overexpression promoted M2 microglial polarization, reduced neuroinflammation, and improved cognitive deficits.
- YY1 inhibited miR-130a-3p, which targets TREM-2, mediating the protective effects of YY1.
Conclusions:
- YY1 promotes M2 microglial polarization by upregulating TREM-2 via interaction with the miR-130a-3p promoter.
- YY1 overexpression represents a potential therapeutic strategy for SAE.
