Downregulation of TRIM27 alleviates hypoxic-ischemic encephalopathy through inhibiting inflammation and microglia cell activation by regulating STAT3/HMGB1 axis.

TRIM27 expression was increased in the Parkinson's disease (PD), and knockdown of TRIM27 in PC12 cells significantly inhibited cell apoptosis, indicating that downregulation of TRIM27 exerts a neuroprotective effect. Herein, we investigated TRIM27 role in hypoxic-ischemic encephalopathy (HIE) and the underlying mechanisms. HIE models were constructed in newborn rats using hypoxic ischemic (HI) treatment and PC-12/BV2 cells with oxygen glucose deprivation (OGD), respectively. The results demonstrated that TRIM27 expression was increased in the brain tissues of HIE rats and OGD-treated PC-12/BV2 cells. Downregulation of TRIM27 reduced the brain infarct volume, inflammatory factor levels and brain injury, as well as decreased the number of M1 subtype of microglia cells while increased the number of M2 microglia cells. Moreover, deletion of TRIM27 expression inhibited the expression of p-STAT3, p-NF-κB and HMGB1 in vivo and in vitro. In addition, overexpression of HMGB1 impaired the effects of TRIM27 downregulation on improving OGD-induced cell viability, inhibiting inflammatory reactions and microglia activation. Collectively, this study revealed that TRIM27 was overexpressed in HIE, and downregulation of TRIM27 could alleviate HI-induced brain injury through repressing inflammation and microglia cell activation via the STAT3/HMGB1 axis.