RNA-seq analysis of pulmonary fibrosis induced by alveolar epithelial mitochondrial ND1 deficiency in rats

In this study, we generated a novel rat model with lung epithelium-specific knockout of the mitochondrial ND1 gene by crossing Sftpc-Cre rats with LSL-DdCBE-ND1 rats. The resulting ND1Sftpc-cre rats spontaneously developed pulmonary fibrosis with restrictive ventilatory defects, metabolic abnormalities, and characteristic histopathological changes including alveolar septal thickening, inflammatory infiltration, and collagen deposition.

To investigate the molecular mechanisms underlying this phenotype, we performed bulk RNA sequencing on lung tissues from ND1Sftpc-crerats and ND1LSL littermate controls. Differential expression analysis identified genes significantly altered in ND1-deficient lungs. Gene Ontology and KEGG pathway enrichment analyses revealed significant upregulation of extracellular matrix (ECM) organization, p53 signaling pathway, and cell cycle-related processes.