αB-crystallin is involved in the process of pulmonary fibrosis

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease with currently no treatment. In the presence of TGF-β, epithelial cells differentiate into myofibroblats, key pro-fibrotic cells in a proccess called epithelial-to-mesemchymal transition (EMT). αB-crystallin belongs to the small heat shock protein family and is constitutively expressed in many tissues including lungs. αB-crystallin is inducible by stress and has a major role in cell cytoskeleton architecture homeostasis by interacting with intermediate filament elements. The role of αB-crystallin in fibrogenesis is unknown. Methods: In vitro we induced EMT on A549 cells after rTGF-β treatment. In vivo, Sprague Dawley rats received intra-tracheal administration of AdTGF-β or AdDL control. SV129 mice wild type (WT) or knock out (KO) for αB-crystallin received intra-tracheal bleomycin (0.07U/mouse). Results: In vitro during TGF-β1-induced EMT: 1. αB-crystallin is early overexpressed, 12 hours before α-SMA overexpression; 2. αB-crystallin colocalize with α-SMA; 3. αB-crystallin interacts with HSP27; 4. The modulation of αB-crystallin plays a role on TGF/SMAD pathway. In vivo: 1. αB-crystallin is overexpressed in fibrotic areas induced by TGF-β overexpression in rats or bleomycin administration in mice; 2. By day 21, collagen accumulation in the lung was significantly higher in WT mice (3 fold increase, p<0.05) compared to KO mice; 3. The level of TGF-β1 was lower in KO mice after bleomycin injection. Conclusion: These results provide evidence that αB-crystallin is involved in pulmonary fibrosis maybe through a role in EMT. This work is supported by the EU, 7th FP, HEALTH-F2-2007-202224 eurIPFnet