Abstract
Epithelial-mesenchymal transition (EMT) is implicated in the pathogenesis of silicosis. High mobility group box 1 (HMGB1) has been found to induce EMT in fibrotic diseases. Previous studies have revealed a critical role of HMGB1 in silicosis, whereas the detail mechanisms still obscure. Here, we observed that HMGB1 protein was increased in the serum of silicosis patients and in the lung tissues of silicotic mice. The levels of HMGB1, receptor for advanced glycation end products (RAGE) and β-catenin protein were increased in the alveolar EMT cell model established by the treatment of transforming growth factor β1 (TGF-β1) and conditioned mediums derived from silica-stimulated macrophages. The activation of HMGB1, RAGE, β-catenin, EMT process, as well as cell migration triggered by TGF-β1 in RLE-6TN cells could be enhanced by treatment with recombinant HMGB1 protein (rHMGB1) and decreased by HMGB1 chemical inhibitor glycyrrhizin or RAGE inhibitor FPS-ZM1. And RAGE suppression could alleviate HMGB1-mediated the aggravation of β-catenin signaling, cell migration and EMT process induced by TGF-β1. Furthermore, both HMGB1 inhibition and RAGE knockout effectively alleviated the lung function impairment, EMT process, pulmonary inflammation and fibrosis in silicotic mice. These findings suggested that HMGB1 might promote EMT through RAGE/β-catenin axis in silicosis. And HMGB1 might constitute a therapeutic target for ameliorating the fibrosis of silicosis.
Published Version
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