Genomic Profile Comparing Epithelial and Underlying Mesenchyme Remodeling in Bleomycin- and BHT-Induced Pulmonary Fibrosis

Context: It is well known that the initiation, distribution, and severity of fibrosis vary among different chemical injuries. However, the mechanisms of chemical variation and their epithelial/mesenchymal basis, as well as the activation of susceptibility to pulmonary fibrosis by profibrotic signals, are poorly investigated. Because of this, we aimed to evaluate and compare the activation profile and perpetuation of fibrosis induced by bleomycin (BLM) and 3-5-di-ieri-4-hydroxytoluene (BHT). Design: For pulmonary fibrosis, groups of male mice (C57Bl/6; n = 6) had BLM (0.1 U) administered by an intratracheal or intraperitoneal route with BHT (400 mg). Sterile saline or corn oil was used as control. Lungs were removed 14 (early) and 21 (late) days after induction, and analysis was performed. All experimental procedures were performed according to the guidelines of the Ethical Committee of the Faculty of Medicine of University of Sao Paulo, Brazil (process code 372/11). Results: Higher amounts of collagen, evaluated by hydroxyproline and Masson staining, were found in BLM and BHT groups when compared to controls (P