Histone deacetylases 3 deletion restrains PM2.5-induced mice lung injury by regulating NF-kappa B and TGF-beta/Smad2/3 signaling pathways

摘要

Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-beta/Smad signaling pathway has been proven to be of significance in fibrosis development. Our results found that PM2.5 induced lung function injury in WT mice with a inflammatory responses through the activation of TGF-beta/Smad signaling pathways, resulting in lung injury. Of note, HDAC3-deficient mice after PM2.5 administration further promoted TGF-beta/Smad signaling pathways activation. In addition, TLR4, p-NF-kappa B and p-I kappa B alpha indicated that HDAC3 knockout mice have a higher inflammation-related signals expression in lung tissue than WT mice after PM2.5 administration, resulting in pro-inflammatory cytokines releasing. Moreover, in vitro experiment of lung epithelial cells challenged with PM2.5, further indicated that TGF-beta/Smad2/3 was involved in fibrosis development, leading to inflammation response. Also, the activation of TLR4/NF-kappa B could be observed in PM2.5-induced lung epithelial cells, leading to inflammation infiltration. These results indicate a new therapeutic target to protect against lung injury caused by PM2.5. (C) 2016 Published by Elsevier Masson SAS.