Transcriptomic differences in lung apices and bases in idiopathic pulmonary fibrosis (IPF)

Abstract

Background: IPF is a progressive lung disease characterized by basally predominant fibrosis. Due to the nature of disease progression, lung tissue at the apices have a lower extent of fibrosis compared to the bases and may represent earlier stage of disease.

Aims: This study compared the transcriptomic profile of lung tissue obtained from lung apices and bases from patients with and without IPF.

Methods: Tissue was collected from matched apex and base of the lungs of 20 patients with IPF and 14 non-diseased control (NDC) donors. Bulk RNA sequencing was performed on a total of 101 samples using the Illumina platform. Differentially expressed genes (DEGs, false discovery rate < 0.05, |fold change| >2) were investigated by performing pathway analysis with Ingenuity Pathway Analysis.

Results: 1055 DEGs (302 downregulated, 753 upregulated) were identified between apices of IPF and NDC. The top 3 pathways enriched in IPF apices (ranked by activation z-score) were organismal development, cell movement and cardiovascular development. 30 common genes amongst the top 3 pathways were involved in macrophage biology. 751 DEGs (98 downregulated, 653 upregulated) were identified between IPF bases and apices. The top 3 pathways enriched in IPF apices were related to inflammation. 1313 DEGs (410 downregulated, 903 upregulated) were identified between bases of IPF and NDC.

Conclusions: Genes regulating macrophages and inflammation were elevated in apices of IPF lung tissue where areas of normal histology also preside. Strategic targeting of pathways involved in IPF lung apices may be more efficacious since the tissue has yet to reach terminal fibrosis.