Abstract
Tissue fibrosis is a major driver of pathology in aging and is involved in numerous age-related diseases. The lungs are particularly susceptible to fibrotic pathology which is currently difficult to treat. The mouse bleomycin-induced fibrosis model was developed to investigate lung fibrosis and widely used over the years. However, a systematic analysis of the accumulated results has not been performed. We undertook a comprehensive data mining and subsequent manual curation, resulting in a collection of 213 genes (available at the TiRe database, www.tiredb.org), which when manipulated had a clear impact on bleomycin-induced lung fibrosis. Our meta-analysis highlights the age component in pulmonary fibrosis and strong links of related genes with longevity. The results support the validity of the bleomycin model to human pathology and suggest the importance of a multi-target therapeutic strategy for pulmonary fibrosis treatment.
Highlights
Tissue fibrosis is a major driver of pathology in aging and is involved in numerous age-related diseases
We first curated a list of genes that when manipulated have been shown to have an impact on the lung fibrosis outcome in bleomycin
Many animal models have far been established for investigating I PF7, the bleomycin model, despite its limitations and disadvantages, is the most widely used and generally viewed as the standard in modeling pulmonary fibrosis[25]
Summary
Tissue fibrosis is a major driver of pathology in aging and is involved in numerous age-related diseases. We undertook a comprehensive data mining and subsequent manual curation, resulting in a collection of 213 genes (available at the TiRe database, www.tiredb.org), which when manipulated had a clear impact on bleomycin-induced lung fibrosis. A systematic analysis of these data has not been performed to date With this in mind, we conducted a meta-analysis of highly curated genes that have been rigorously shown to impact lung fibrosis in the bleomycin mouse model. We conducted a meta-analysis of highly curated genes that have been rigorously shown to impact lung fibrosis in the bleomycin mouse model The list containing these pulmonary fibrosis-related genes (PFRGs) is part of the TiRe database (http://www.tiredb.org), which contains curated genetic information on wound healing and fibroproliferative p rocesses[15]. Apart from the collection and detailed characterization of PFRGs, we placed a special emphasis on (i) the consistency between different types of manipulations; (ii) the consistency of bleomycin data with the expression of corresponding genes in lungs of IPF patients, and (iii) the relationships between lung fibrosis-related and longevity-associated genes (LAGs)
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