Exploration of micro RNA regulating lung fibrosis and epithelial mesenchymal transition

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To determine the role of epithelial Pten in lung fibrosis, we compared the responses to bleomycin administration between wild-type and bronchioalveolar epithelium-specifically Pten-deleted[SP-C-rtTA/(tetO)_7-Cre/Pten^Δ/Δ(SOPten^Δ/Δ) mouse. Epithelial-derived myofibroblasts were increased in epithelium-specific Pten-deficient mice. Lungs of bleomycin-treated SOPten^Δ/Δmice showed increased pAkt, pS6K, Snai expressions. Akt inactivation definitively saved SOPtenΔ/Δmice. Finally, we detected a reduction of PTEN expression and AKT hyperactivation in the AECs of human IPF lungs. Our results highlight epithelial Pten as a crucial gatekeeper controlling lung fibrosis by modulating integrity of AECs.