HMGB1 induces lung fibroblast to myofibroblast differentiation through NF‑κB‑mediated TGF‑β1 release.

Abstract

The proinflammatory factor high-mobility group box protein 1 (HMGB1) has been implicated in the pathogenesis of lung fibrosis; however, the role of HMGB1 in lung fibrosis remains unclear. It has previously been reported that nuclear factor (NF)-κB and transforming growth factor (TGF)-β1 may be involved in lung fibrosis. Therefore, the present study aimed to examine the potential molecular mechanisms that underlie HMGB1-induced lung fibrosis via the regulation of NF-κB and TGF-β1. The results demonstrated that HMGB1 stimulation increased the activation of NF-κB and the release of TGF-β1, as well as the expression of α-smooth muscle actin (α-SMA) and collagen I in human lung fibroblasts in vitro. In addition, inhibition of NF-κB activation blocked HMGB1-induced TGF-β1 release, as well as α-SMA and collagen I expression in lung fibroblasts. Preventing the release of TGF-β1 inhibited HMGB1-induced α-SMA and collagen I expression; however, it had no effect on NF-κB activation. Collectively, these findings indicate that HMGB1 induces fibroblast to myofibroblast differentiation of lung fibroblasts via NF-κB-mediated TGF-β1 release.