novel development research on the prevention and treatment of pulmonary fibrosis

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We recently reported two substances (ATRA and thalidomide) had preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β_1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that Calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of Rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis.Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β_1, angiopoietin-1, and collagen type Iα1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced 1) production of IL-6, TGF-β_1, angiopoietin-1 and collagen synthesis from lung fibroblasts, and 2) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis.These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis.