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

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)-kappa B and transforming growth factor (TGF)-beta 1 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-kappa B and TGF-beta 1. The results demonstrated that HMGB1 stimulation increased the activation of NF-kappa B and the release of TGF-beta 1, as well as the expression of alpha-smooth muscle actin (alpha-SMA) and collagen I in human lung fibroblasts in vitro. In addition, inhibition of NF-kappa B activation blocked HMGB1-induced TGF-beta 1 release, as well as alpha-SMA and collagen I expression in lung fibroblasts. Preventing the release of TGF-beta 1 inhibited HMGB1-induced alpha-SMA and collagen I expression; however, it had no effect on NF-kappa B activation. Collectively, these findings indicate that HMGB1 induces fibroblast to myofibroblast differentiation of lung fibroblasts via NF-kappa B-mediated TGF-beta 1 release.