title: Repression of a chromatin modifier aggravates lipopolysaccharide-induced acute lung injury in mouse.
abstract: Local inflammatory responses and alveolar epithelial cells (AECs) apoptosis are both important for the development of the acute lung injury (ALI), a clinically important complication causing high morbidity and mortality, but little is known about the molecular mechanisms underlying the pathogenesis. Herein, we showed for the first time that expression of Metastasis-associated protein 1 (MTA1), a master transcriptional regulator with the ability to regulate divergent cellular pathways by modifying the acetylation status of crucial target genes, was up-regulated in the alveolar cells of the Escherichia coli lipopolysaccharide (LPS)-induced murine ALI model. Inhibition of MTA1 expression by in vivo siRNA treatment exacerbated the pathology of LPS-induced ALI, by selectively promoting the expression of NF-κB-regulated inflammatory cytokines. Moreover, ablation of MTA1 expression promoted the LPS-induced apoptosis in AEC II cells, leaving AEC I cells unaffected. These data collectively underscore an alveolar facet of this important chromatin modifier, which may represent as a novel regulator and a new therapeutic target for the treatment of ALI.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Jia-kuan
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Wen-chen
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zang
authors.affiliation: Department of Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China. Electronic address: liweipepeyato@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Electronic address: jiangtaochest@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004926:Escherichia coli; D005260:Female; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D016207:Cytokines; D008070:Lipopolysaccharides; C503336:Mta1 protein, mouse; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors
keywords: Acute lung injury; Alveolar epithelial cells; Apoptosis; Lipopolysaccharide; Metastasis-associated protein 1; NF-κB