LAUSR

PURPOSE Sepsis-associated encephalopathy (SAE) induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation. Yin Yang 1 (YY1) is an important transcription factor which 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 (CLP) 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 and TREM-2 were 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.