Global Profiling of Proteome, Lysine Acetylome And Succinylome Identifying Silica Injuries In Mice Lung

Abstract

BackgroundCrystalline silica dust (CSD) inhalation induces incurable lung damage, silicosis and idiopathic pulmonary fibrosis. However, the injury mechanisms remain poor, with limited therapeutic options aside from lung transplantation.ResultsCombined quantitative proteome, acetylome, and succinylome were performed with bioinformatic analysis of lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Here, we created the largest proteome, acetylome and succinylome datasets in silica-injured lungs with mice model to date, identifying 8,867 proteins and quantified 6,870. Additionally, 3,472 acetylated sites within 1,698 proteins and 4,313 succinylated sites within 2,209 proteins were identified. Our enrichment results suggested that efferocytosis, metabolism dysregulation and vascular remodeling participate in silica injury, and acetylation as well as succinylation play important roles in the pathophysiological changes. Furthermore, we applied integrated analysis between proteome, acetylome and succinylome, then constructed the protein landscape within our datasets. Finally, we validated the significant potential biomarkers with mice and human samples. ConclusionTaken together, this report reveals the most comprehensive landscape in silica-injured mouse, and presents novel understanding of the molecular pathological process for silica-induced lung diseases.