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

Peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ is inversely correlated with that of high mobility group box 1 (HMGB1, a late proinflammatory mediator) in patients with sepsis. Activation of PPARγ inhibits the basal and LPS-induced expression of HMGB1. The PPARγ-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 PPARγ-induced miR-142-3p suppresses inflammatory response in vivo. These results suggest that PPARγ-mediated upregulation of miR-142-3p inhibits the HMGB1 expression, which, in turn, is a novel anti-inflammatory mechanism of PPARγ and has an important role in the treatment of inflammatory diseases.