Asthma is a heterogeneous pulmonary disorder, the progression and chronization of which leads to
airway remodeling and fibrogenesis. To understand the molecular mechanisms of
pulmonary fibrosis development, key genes forming the
asthma-specific regulome and involved in lung
fibrosis formation were revealed using a comprehensive bioinformatics analysis. The bioinformatics data were validated using a murine model of
ovalbumin (OVA)-induced
asthma and post-asthmatic
fibrosis. The performed analysis revealed a range of well-known pro-fibrotic markers (Cat, Ccl2, Ccl4, Ccr2, Col1a1, Cxcl12, Igf1, Muc5ac/Muc5b, Spp1, Timp1) and a set of novel genes (C3, C3ar1, Col4a1, Col4a2,
Cyp2e1, Fn1, Thbs1, Tyrobp) mediating fibrotic changes in lungs already at the stage of acute/subacute
asthma-driven
inflammation. The validation of genes related to non-allergic
bleomycin-induced
pulmonary fibrosis on asthmatic/fibrotic lungs allowed us to identify new universal genes (Col4a1 and Col4a2) associated with the development of lung
fibrosis regardless of its etiology. The similarities revealed in the expression profiles of nodal fibrotic genes between
asthma-driven
fibrosis in mice and nascent
idiopathic pulmonary fibrosis in humans suggest a tight association of identified genes with the early stages of
airway remodeling and can be considered as promising predictors and early markers of
pulmonary fibrosis.