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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
PGC-1-related coactivator (PRC) is an important regulator of microglia M2 polarization
Chengzhi Mou1, Bin Liu1, Ming Wang1
1Department of Neurosurgery, Shandong Provincial Hospital affiliated to Shandong University, 9677 Jingshi Road, Jinan, Shandong, 250021, China.
Abstract:
Microglia can be driven to adopt M1 and M2 phenotypes. While the distinct functions of M1 and M2 microglia have been intensively studied, the former are considered proinflammatory and the latter anti-inflammatory. PGC-1-related coactivator (PRC), an important member in the peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family, plays an essential role in metabolic regulation and cell proliferation. The effects of PRC on microglia M2 polarization are still unknown. In this study, we found that PRC expression was robustly induced in M2 microglia. Overexpression of PRC promotes microglia M2 polarization by increasing the expression of arginase-1 (Arg1), resistin-like α (Retnla, Fizz1), and chitinase 3-like 3 (Chi3l3, Ym1). In contrast, the silence of PRC attenuates microglia M2 polarization. Mechanistically, PRC was found to cooperate with signal transducer and activator of transcription 6 (STAT6) to induce an M2 genetic program. Overall, our findings identify PRC as what we believe to be a novel regulator of microglia M2 polarization.
Insights
PGC-1-related coactivator (PRC) promotes anti-inflammatory M2 microglia polarization. PRC, working with STAT6, drives M2 gene expression, identifying it as a novel regulator of microglia phenotypes.
Area of Science:
- Neuroimmunology
- Cellular Metabolism
Background:
- Microglia, the immune cells of the central nervous system, exhibit M1 (proinflammatory) and M2 (anti-inflammatory) phenotypes.
- The role of PGC-1-related coactivator (PRC) in regulating microglia polarization, particularly M2 phenotype, remains largely unexplored.
Purpose of the Study:
- To investigate the role of PRC in microglia M2 polarization.
- To elucidate the molecular mechanisms by which PRC influences M2 microglia phenotypes.
Main Methods:
- Overexpression and silencing of PRC in microglia.
- Quantitative analysis of M2 marker gene expression (Arg1, Retnla/Fizz1, Chi3l3/Ym1).
- Investigation of PRC interaction with STAT6.
Main Results:
- PRC expression is significantly upregulated in M2 microglia.
- Overexpression of PRC enhances M2 polarization, increasing key M2 markers.
- PRC silencing reduces M2 polarization.
- PRC cooperates with STAT6 to promote an M2 genetic program.
Conclusions:
- PRC is identified as a novel and positive regulator of microglia M2 polarization.
- PRC, in conjunction with STAT6, orchestrates the M2 microglia phenotype.
- These findings offer new insights into metabolic regulation of neuroinflammation.
