Study On The Mechanism Of The Protective Effect Of Feifukang In Pulmonary Fibrosis

This Context:An abnormal high mobility group box 1 (HMGB1) activation plays an important role in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (FFK) has very good lung protection in clinical use which is extracted from eight kinds of traditional Chinese medicines. However, whether FFK has anti-fibrotic function is unknown.Objective:In this study, we investigated the effects of FFK on transforming growth factor-?1(TGF-?1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in in vitro and in vivo.Materials and methods:The effects of FFK on the transforming growth factor-?1 (TGF-?1)-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated.Results:FFK treatment resulted in a reduction of EMT in A549 cells with attenuating the increase of vimentin, whereas attenuating the decrease of E-cadherin. FFK inhibited the proliferation of HLF1 with the IC50 is 0.51?g/ml. FFK ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological score and collagen deposition, and a lower a-smooth muscle actin (a-SMA) and HMGB1 expression, whereas higher receptor for advanced glycation end-product (RAGE) was found in BLM-instilled lungs. FFK significantly reversed the EMT and prevented pulmonary fibrosis through decreasing HGMB1 and regulating RAGE in vitro and in vivo.Discussion and conclusion:FFK inhibit the TGF-?1-induced EMT via decreasing HMGB1 and vimentin, whereas increasing RAGE and E-cadherin levels. In summary, the results demonstrate that FFK prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway.An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play an key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-?1(TGF-?1)-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, a-smooth muscle actin (a-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation'of RAGE, PA reversed the EMT, inhibited HLF1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway.