Mucus matters: Ferrets demonstrate sustained fibrosis and mucociliary decrement following bleomycin-induced pulmonary fibrosis

摘要: Intro: A gain-of-function promoter variant for MUC5B is the strongest risk factor development of idiopathic pulmonary fibrosis (IPF); yet, role in IPF pathogenesis unknown. Ferrets and humans have a similar distribution production lung. Obj: Determine if bleomycin(BL)-exposed ferrets develop features resembling elucidate mucociliary clearance (MCC). Methods: BL (5U/kg) or saline control (SCt) was administered IT to ferrets. Fibrosis assessed with μCT, hydroxyproline (Hyp), SHG histology. Muc5B, a-SMA, acetylated tubulin CCSP expression were by IHC IF. MC transport (MCT) ciliary beat frequency (CBF) ex-vivo using μOCT. MCC vivo SPECT/CT imaging Tc99-DTPA. Results: Apparent at 2wks, ground-glass opacities persisted through 6wks on μCT. Volumetric μCT analysis revealed increased lungs (increased 18.1±2.2% vs -0.8±0.8% SCt, P Conclusion: BL-exposed exhibit not seen rodents: FF, mucin-rich honeycomb cysts, bronchiolized distal airspaces, sustained associated aberrant MCT.