Molecular network of important genes for systemic sclerosis-related progressive lung fibrosis

Abstract

Background: Considerable progress has been made in illuminating the pathological events for systemic sclerosis (SSc)-related progressive lung fibrosis. The molecular events that lead to SSc-related progressive lung fibrosis need to be defined. Some important genes have been identified from a recent study in humans. We aim to construct and compare the similarities and differences of molecular pathways between SSc-related progressive lung fibrosis and normal lungs of humans and mice. Methods: We used the analytical approach of association of key genes in SSc-related progressive lung fibrosis. We first identified the probes for genes of SSc-related progressive lung fibrosis and analyzed the pathways in human lung using data generated by microarray. We then analyzed the gene pathways in mouse lung for similar sets of probes. Gene expression data from livers were used to compare with that in lung in both humans and mice. Results: Our analysis indicated that, in humans, the expression levels of genes for macrophage activation are more strongly associated with each other than that in mice. In both humans and mice, the associations of these genes are much greater in the lung than that in the liver. The association in gene expression between humans and mice are similar for IFN-regulated genes and profibrotic/Tgfβ-regulated genes. Conclusion: Our analysis reveals the differences and similarities of the network of key genes between humans and mice during the molecular processes that eventually lead to fibrosis in the lung.