title: Histone deacetylases 3 deletion restrains PM2.5-induced mice lung injury by regulating NF-κB and TGF-β/Smad2/3 signaling pathways.
abstract: 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-β/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-β/Smad signaling pathways, resulting in lung injury. Of note, HDAC3-deficient mice after PM2.5 administration further promoted TGF-β/Smad signaling pathways activation. In addition, TLR4, p-NF-κB and p-IκBα 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-β/Smad2/3 was involved in fibrosis development, leading to inflammation response. Also, the activation of TLR4/NF-κB 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.
authors.affiliation: Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu 223002, China. Electronic address: yu197301@yeah.net.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Gu
authors.affiliation: Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu 223002, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, Huai'an Second People's Hospital, Nanjing Medical University, Jiangsu 223002, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D016328:NF-kappa B; D052638:Particulate Matter; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D000099186:Histone Deacetylase 3; C497783:Smad2 protein, mouse; C497791:Smad3 protein, mouse
keywords: Acute lung injury; HDAC 3; PM2.5; TGF-β/Smad; TLR4/NF-κB