Central Lung Gene Expression Associates with Myofibroblast Activity in Idiopathic Pulmonary Fibrosis

Non-fibrotic central regions of IPF lungs demonstrate massive dysregulated gene expression involving enhanced T-cell differentiation, pulmonary fibrosis idiopathic, and wound healing pathways. Enhancement of myofibroblast features without apparent extra-cellular matrix deposition in the central non-fibrotic region of IPF lungs renders a window for cell-based molecular targeting therapy. IPF lungs were grossly examined within 6-12 hours from the time of explant, and multiple 1cm3 biopsies were obtained from macroscopically non-fibrotic central (IPF.C) and fibrotic peripheral (IPF.P) areas. Non-IPF donor lung biopsies of central (CTR.C) and peripheral (CTR.P) were similarly obtained. H&E-stained biopsies were reviewed and confirmed by two clinical pulmonary pathologists (Jefree Schulte, Aliya Husain). Representative central and peripheral samples from IPF patients and non-IPF donors were selected and underwent pathologic classification and scoring to quantify fibrosis, fibroblastic foci, honeycombing, inflammation, and pulmonary hypertension.