PPARγ inhibits HMGB1 expression through upregulation of miR-142-3p in vitro and in vivo

Peroxisome proliferator-activated receptor gamma (PPAR gamma) belongs to the nuclear receptor superfamily and it has received much attention because of its anti-inflammatory activity. However, the underlying molecular mechanism is not completely understood. In the present study, we demonstrated that the level of PPAR gamma is inversely correlated with that of high mobility group box 1 (HMGB1, a late proinflammatory mediator) in patients with sepsis. Activation of PPAR gamma inhibits the basal and LPS-induced expression of HMGB1. The PPAR gamma-mediated inhibition of HMGB1 is associated with the upregulation of miR-142-3p, which can target the 3'-UTR of HMGB1, by directly binding to the PPRE in the miR-142-3p promoter region. Functional experiments reveal that the PPAR gamma-induced miR-142-3p suppresses inflammatory response in vivo. These results suggest that PPAR gamma-mediated upregulation of miR-142-3p inhibits the HMGB1 expression, which, in turn, is a novel anti-inflammatory mechanism of PPAR gamma and has an important role in the treatment of inflammatory diseases. (C) 2015 Elsevier Inc. All rights reserved.