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

ABSTRACT: 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.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.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/Tgf?-regulated genes.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.

SUBMITTER: Jiao Y

PROVIDER: S-EPMC4596290 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Jiao Yan Y Chen Hong H Gu Tianshu T Wang Lishi L Postlethwaite Arnold A Gu Weikuan W

BMC research notes 20151007

<h4>Background</h4>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.<h4>Met ...[more]

PMID: 26444860

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Project description:OBJECTIVE: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. METHODS: Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2-3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. RESULTS: Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)- and interferon (IFN)-regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < -0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. CONCLUSION: These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and activation, and up-regulated expression of TGFβ- and IFN-regulated genes

Dataset Information

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

Publications

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

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