Asthma and Post-Asthmatic Fibrosis: A Search for New Promising Molecular Markers of Transition from Acute Inflammation to Pulmonary Fibrosis
2022
Innokenty A. Savin | Andrey V. Markov | Marina A. Zenkova | Aleksandra V. Sen’kova
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 (<i>Cat</i>, <i>Ccl2</i>, <i>Ccl4</i>, <i>Ccr2</i>, <i>Col1a1</i>, <i>Cxcl12</i>, <i>Igf1</i>, <i>Muc5ac/Muc5b</i>, <i>Spp1</i>, <i>Timp1</i>) and a set of novel genes (<i>C3</i>, <i>C3ar1</i>, <i>Col4a1</i>, <i>Col4a2</i>, <i>Cyp2e1</i>, <i>Fn1</i>, <i>Thbs1</i>, <i>Tyrobp</i>) 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 (<i>Col4a1</i> and <i>Col4a2</i>) 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.
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