Alteration in the transcriptome of lung basal epithelial cells isolated from IPF lungs upon genetic knockdown of SOX9

Pulmonary fibrosis (PF) is associated with various chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), systemic sclerosis (SSc), and cystic fibrosis (CF). It is characterized by the progressive accumulation of mesenchymal cells and excessive extracellular matrix production (ECM), resulting in scar tissue formation. PF arises from a dysregulated response to alveolar injury, leading to a progressive decline in lung function that remains largely unresponsive to current pharmacological therapies. Both airway and alveolar epithelial cells, along with mesenchymal cells, contribute to PF, but the cell-specific pathways and gene networks driving the pathophysiology remain poorly understood. Our recent findings indicate abnormal activation of SOX9 in lung basal epithelial cells from IPF lung biopsies and in a mouse model of repetitive bleomycin-induced fibrosis. In this study, we aimed to determine the role of SOX9 in regulating transcriptomic changes in basal epithelial cells during pulmonary fibrosis. Our results show that SOX9 governs the transcriptional programs involved in basal epithelial cell differentiation to mucus producing goblet cells, and inflammation. In conclusion, this study demonstrates that SOX9 is a critical regulator of basal cell dysfunction in IPF and represents a potential target for therapeutic intervention. Overall design: mRNA profiles of cultured fibrotic lung resident distal basal epithelial cells isolated from IPF lungs and treated with either Control or SOX9-specific siRNA