title: Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo.
abstract: Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lv
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects; D045424:Complex Mixtures / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D024243:HMGB1 Protein / Q000187:drug effects; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000187:drug effects; D015203:Reproducibility of Results; D053773:Transforming Growth Factor beta1 / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D045424:Complex Mixtures; D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; D010982:Platelet-Derived Growth Factor; D000067759:Receptor for Advanced Glycation End Products; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D003094:Collagen; D006909:Hydroxyproline