Transcriptomic profiling of collagen gene expression in lung fibroblasts from patients with idiopathic pulmonary...

Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant extracellular matrix remodeling. While type I and III collagens are known contributors, the broader transcriptional landscape of diverse collagen genes in IPF fibroblasts and their potential associations with clinical outcomes remain incompletely understood. This study aimed to comprehensively characterize gene expression of collagen genes in IPF fibroblasts and to explore its relationship with patient survival.

RNA sequencing was conducted on primary lung fibroblasts from 33 IPF patients and 10 non-fibrotic controls. Differential expression of collagen genes was analyzed using EdgeR's exact test, with significance defined as false discovery rate-adjusted p < 0.05. Association with mortality was assessed using Cox regression analysis.

Among 17 collagen genes, 14 genes - including COL1A1, COL1A2, COL3A1, COL4A4, COL4A5, COL4A6, COL5A2, COL6A6, COL8A1, COL11A1, COL14A1, COL18A1, COL24A1, and COL27A1 - were significantly upregulated in IPF fibroblasts, while COL5A3, COL13A1, and COL16A1 were downregulated. COL3A1, COL4A4, and COL24A1 were associated with reduced survival in both Cox regression analysis and Kaplan-Meier plots. Among them, COL4A4 remained association with mortality in multivariable Cox model.

This study delineates fibroblast-specific dysregulation across multiple collagen families in IPF, providing mechanistic insight into extracellular matrix remodeling. Although COL4A4 remained associated with mortality in multivariable Cox models, this finding should be interpreted as exploratory, given the limited number of events and the absence of experimental validation. Overall, our results highlight collagen transcript signatures as hypothesis-generating markers that warrant further validation to clarify their potential clinical relevance in IPF.