Researchers Identify Potential Genetic Pathways of Systemic Sclerosis-Associated Pulmonary Fibrosis

Bruno Castro, PhD avatar

by Bruno Castro, PhD |

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In a recent study entitled “Molecular network of important genes for systemic sclerosis-related progressive lung fibrosis”, published in the BMC Research Notes journal, a team of researchers from the US and China established the expression levels of crucial genes for Systemic Sclerosis-related progressive pulmonary fibrosis in human and mouse lungs. These findings show why lungs are more susceptible to fibrosis in systemic sclerosis and might help on the development of improved therapies.

Systemic sclerosis is a rare autoimmune disorder characterized by the deposition of collagen in the skin and internal organs due to the unregulated functioning of the body’s own immune system. Disease severity and mortality are intrinsically related with the extent of internal tissue damage, being systemic sclerosis-related pulmonary fibrosis one of the leading causes of death in these patients. Recently, the inflammatory genes involved in pulmonary fibrosis development in systemic sclerosis patients have been identified. Knowing how these genes are connected and regulated is important for disease diagnostic and to understand what are the molecular mechanisms underlying disease progression.

In the study, authors identified key genes in systemic sclerosis-derived pulmonary fibrosis and used an analytical approach to quantify their expression levels, association and gene network in lungs and liver of normal, healthy humans. Furthermore, the team also investigated these gene pathways in mouse lungs and compared the results to those gathered in humans, to comprehend whether disease progression has common roots in humans and animals.

The analysis showed a strong association between the expression levels of genes linked to macrophage activation, IFN-regulated, and profibrotic/Tgfβ-regulated inflammatory genes in healthy human lungs. In mice lungs, only IFN-regulated and profibrotic/Tgfβ-regulated genes were found to be strongly associated, highlighting the need to identify differences between humans and animal models in translational clinical studies. Nonetheless, in both humans and in mice, pro-inflammatory genes association is stronger in the lung than in the liver. This finding show why lungs are more severely affected in systemic sclerosis.

Due to the intimate association between lung inflammatory genes, dysregulation of one of these genes will impact the expression levels of other genes, contributing for the establishment of an inflammatory condition and subsequent lesions. The potential molecular pathways for systemic sclerosis-associated lung fibrosis unveiled by the researchers advances our understanding of the molecular mechanisms underlying disease development. Further studies are, however, needed to verify these results and identify the sequence of events regulating the inflammatory genes expression in patients’ lungs. These will certainly facilitate the identification of potential drug targets and the development of effective therapies.