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Development of gene expression signatures of murine silicosis in the lung CD45-negative tissue cells from CCR2 knockout mice

ABSTRACT: Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although macrophages are known to promote both the initiation and resolution of lung injury in reversible PF, it remains unclear how macrophages contribute to the progression of chronic PF. The object of this study was to investigate the role of inflammatory monocyte-derived macrophages (MMs) in the transcriptomic signatures of the lung tissue cells from murine progressive PF. We collected CD45-negative lung tissue cells from silica-treated CCR2 knockout and WT mice on days 28, 40 and untreated mice on day 0 post-aspiration and performed global transcriptome analyses using microarray. Data were analyzed by fuzzy c-means or CLICK clustering, gene set enrichment analysis, and network analyses. Global transcriptome analyses revealed that MM deficiency potentiated changes in gene-expression in tissue cells, closely matching trends seen in human chronic PF. Regulatory network analysis of transcriptome data suggested that MM-derived factors, such as tumor necrosis factor-α, were involved in the suppression of tissue remodeling-related gene expression. Overall, these results demonstrate that MMs suppress tissue cell responses and associated pathology in progressive PF.

ORGANISM(S): Mus musculus

PROVIDER: GSE61709 | GEO | 2016/09/24

SECONDARY ACCESSION(S): PRJNA261936

REPOSITORIES: GEO

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