Effect of HSP47siRNA targeting to the lung myofibroblast on bleomycin-induced pulmonary fibrosis

Research Project

Project/Area Number	21790777
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Respiratory organ internal medicine
Research Institution	Sapporo Medical University
Principal Investigator	OTSUKA Mitsuo Sapporo Medical University, 医学部, 助教 (10398323)
Project Period (FY)	2009 – 2010
Project Status	Completed (Fiscal Year 2010)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords	肺線維症 / HSP47 / siRNA
Research Abstract	Expression of HSP47 increases in parallel with expression of collagens during the progression of lung fibrosis. Myofibroblasts are increased in active lung fibrotic areas and overexpress of the HSP47. It is expected that to control of the expression of the HSP47 in the myofibroblasts may reduce of the lung fibrosis. To investigate whether inhibition of HSP47 of the myofibroblasts with siRNA could have beneficial effects in rat bleomycin lung fibrosis models. We made rat bleomycin lung fibrosis models and injected of vitaminA-coupled liposomes carrying HSP47siRNA in rat tail vein. In rats treated with vitaminA-coupled liposomes carrying siRNA, lung fibrosis was significantly improved morphological changes and the increase of the contents of the lung hydroxyproline. Furthermore the increase of the inflammatory cytokines was reduced and the myofibroblasts were induced to apoptosis. These results suggest that HSP47siRNA improves bleomycin lung fibrosis and this drug delivery system using the vitaminA are useful methods.