TY - JOUR T1 - HSP47siRNA targeting to myofibroblasts attenuates bleomycin-induced pulmonary fibrosis JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - 4533 AU - Mitsuo Otsuka AU - Masanori Shiratori AU - Koji Kuronuma AU - Hiroki Takahashi Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/4533.abstract N2 - Rationale:The 47-kDa heat shock protein 47 (HSP47) plays a role in the processing of procollagens as a collagen molecular chaperone. The HSP47-positive cells increase in lung fibrosis, which suggests an important role of HSP47 in the pathogenesis of lung fibrosis. It is expected that to control the expression of the HSP47 may reduce the lung fibrosis. Lung myofibroblasts are speculated vitamin A (VA)-storing cells in the lungs like hepatic stellate cells. Based on these properties of myofibroblasts, we prepared a VA-coupled liposomes carrying HSP47siRNA. The goal of this study is to investigate whether the inhibition of HSP47 for the myofibroblasts with siRNA influences to lung fibrosis.Methods:Sprague-Dawley male rats were treated with intra-tracheal bleomycin (BLM) or PBS. We injected VA-coupled liposomes carrying HSP47siRNA into rat tail vein three times in a week. We made 5 groups; PBS intratracheally & PBS intravenously, BLM & PBS, BLM & VA-HSP47siRNA, BLM & HSP47siRNA, and BLM & VA-randomRNA, respectively. We measured the contents of lung hydroxyproline, BAL cells counts, HSP47 expression, and cytokines.Results:Western blotting showed the expressions of HSP47 were reduced in rats treated with VA-coupled liposomes carrying HSP47siRNA. The liposomes with HSP47siRNA significantly improved lung fibrosis morphologically and the increases of hydroxyproline contents in the lungs, the inflammatory cytokines, and the number of BAL cells.Conclusions:These results suggest that HSP47siRNA improves bleomycin-induced lung fibrosis and this drug delivery system is useful methods. ER -