Transcriptomic changes driving pulmonary fibrosis resolution in young and old Bleomycin-treated mice

Bleomycin-induced pulmonary fibrosis in mice mimics major hallmarks of idiopathic pulmonary fibrosis, yet in this model it spontaneously resolves over time. We studied molecular mechanisms of fibrosis resolution and lung repair, focusing on transcriptional and proteomic signatures and the effect of aging. Old mice showed delayed and incomplete lung function recovery 8 weeks after Bleomycin instillation. This shift in structural and functional repair in old Bleomycin-treated mice was reflected in a temporal shift in gene and protein expression. We reveal gene signatures and signaling pathways which underpin the lung repair process. Male mice (Mus musculus), strain C57BL/6J, age 8 – 12 weeks (young) and 21 months (old) were subjected to Bleomycin intratracheal instillation or control saline (NaCl) treatment, sacrificed on days 0, 14, 21, 28, 35, 42 and 56. Subsequently, lungs were dissected flash frozen in liquid nitrogen, homogenized, and upon RNA-isolation and library preparation, RNA-seq was performed. Transcriptomics and proteomics data were analysed in order to follow resolution of pulmonary fibrosis and lung repair over time and to elucidate age-related differences.