PGC-1-related coactivator (PRC) is an important regulator of microglia M2 polarization.

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.