1. Academic Validation
  2. Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages

Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages

  • Cells. 2020 Jan 4;9(1):122. doi: 10.3390/cells9010122.
Xiu He 1 Shi Chen 2 Chao Li 1 Jiaqi Ban 1 Yungeng Wei 1 Yangyang He 1 Fangwei Liu 1 Ying Chen 1 Jie Chen 1
Affiliations

Affiliations

  • 1 Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
  • 2 School of Medicine, Hunan Normal University, No.36 Lushan Road, Changsha 410013, China.
Abstract

Silicosis is an occupational lung disease characterized by persistent inflammation and irreversible fibrosis. Crystalline silica (CS) particles are mainly phagocytized by alveolar macrophages (AMs), which trigger Apoptosis, inflammation, and pulmonary fibrosis. Previously, we found that autophagy-lysosomal system dysfunction in AMs was involved in CS-induced inflammation and fibrosis. Induction of Autophagy and lysosomal biogenesis by transcription factor EB (TFEB) nuclear translocation can rescue fibrotic diseases. However, the role of TFEB in silicosis is unknown. In this study, we found that CS induced TFEB nuclear localization and increased TFEB expression in macrophages both in vivo and in vitro. However, TFEB overexpression or treatment with the TFEB activator trehalose (Tre) alleviated lysosomal dysfunction and enhanced autophagic flux. It also reduced Apoptosis, inflammatory cytokine levels, and fibrosis. Both pharmacologically inhibition of Autophagy and TFEB knockdown in macrophages significantly abolished the antiapoptotic and anti-inflammatory effects elicited by either TFEB overexpression or Tre treatment. In conclusion, these results uncover a protective role of TFEB-mediated Autophagy in silicosis. Our study suggests that restoration of autophagy-lysosomal function by Tre-induced TFEB activation may be a novel strategy for the treatment of silicosis.

Keywords

TFEB; alveolar macrophages; autophagy; lysosome; silicosis; trehalose.

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