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Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo.

Zhang L, Ji YX, Jiang WL, Lv CJ - Braz. J. Med. Biol. Res. (2015)

Bottom Line: 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.An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs.PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.

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.

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Effects of pulmonary rehabilitation mixture (PRM) on α-smooth muscle actin(α-SMA), fibroblast growth factor (FGF)-2, platelet-derived growth factor(PDGF), high mobility group protein B1 (HMGB1), and receptor for advancedglycation end-product (RAGE) expression in bleomycin (BLM)-treated animals.Representative light microscopic appearance of α-SMA and HMGB1 in lung tissue(immunostaining) for the normal (A1, B1), themodel (A2, B2), and 3 g/kg PRM(A3, B3). C,Representative Western blots of α-SMA, FGF-2, PDGF, HMGB1 and RAGE.D, E, Effects of PRM on α-SMA, FGF-2,PDGF, HMGB1 and RAGE expression in BLM-treated lung by Western analysis. Dataare reported as means±SD. PCNA: proliferating cell nuclear antigen.#P<0.01 vs the normal group; *P<0.01vs the model group (one-way ANOVA followed by Dunnett'stest).
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f06: Effects of pulmonary rehabilitation mixture (PRM) on α-smooth muscle actin(α-SMA), fibroblast growth factor (FGF)-2, platelet-derived growth factor(PDGF), high mobility group protein B1 (HMGB1), and receptor for advancedglycation end-product (RAGE) expression in bleomycin (BLM)-treated animals.Representative light microscopic appearance of α-SMA and HMGB1 in lung tissue(immunostaining) for the normal (A1, B1), themodel (A2, B2), and 3 g/kg PRM(A3, B3). C,Representative Western blots of α-SMA, FGF-2, PDGF, HMGB1 and RAGE.D, E, Effects of PRM on α-SMA, FGF-2,PDGF, HMGB1 and RAGE expression in BLM-treated lung by Western analysis. Dataare reported as means±SD. PCNA: proliferating cell nuclear antigen.#P<0.01 vs the normal group; *P<0.01vs the model group (one-way ANOVA followed by Dunnett'stest).

Mentions: α-SMA was stained in the cytoplasm, while HMGB1 was stained in the nucleus in thelung tissue, which stained brown for immunohistochemistry, as shown in Figure 6. A smaller amount of α-SMA and HMGB1 wasfound in PRM-treated rats compared to the BLM-treated rats. FGF2, α-SMA, PDGF, HMGB1and RAGE in lung tissue were analyzed by Western blot, as shown in Figure 6. The results showed that FGF2, PDGF,α-SMA, HMGB1 and RAGE were all decreased in the PRM rats. It showed that PRMinhibited the EMT and fibroblast proliferation in vitro andin vivo.


Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo.

Zhang L, Ji YX, Jiang WL, Lv CJ - Braz. J. Med. Biol. Res. (2015)

Effects of pulmonary rehabilitation mixture (PRM) on α-smooth muscle actin(α-SMA), fibroblast growth factor (FGF)-2, platelet-derived growth factor(PDGF), high mobility group protein B1 (HMGB1), and receptor for advancedglycation end-product (RAGE) expression in bleomycin (BLM)-treated animals.Representative light microscopic appearance of α-SMA and HMGB1 in lung tissue(immunostaining) for the normal (A1, B1), themodel (A2, B2), and 3 g/kg PRM(A3, B3). C,Representative Western blots of α-SMA, FGF-2, PDGF, HMGB1 and RAGE.D, E, Effects of PRM on α-SMA, FGF-2,PDGF, HMGB1 and RAGE expression in BLM-treated lung by Western analysis. Dataare reported as means±SD. PCNA: proliferating cell nuclear antigen.#P<0.01 vs the normal group; *P<0.01vs the model group (one-way ANOVA followed by Dunnett'stest).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470314&req=5

f06: Effects of pulmonary rehabilitation mixture (PRM) on α-smooth muscle actin(α-SMA), fibroblast growth factor (FGF)-2, platelet-derived growth factor(PDGF), high mobility group protein B1 (HMGB1), and receptor for advancedglycation end-product (RAGE) expression in bleomycin (BLM)-treated animals.Representative light microscopic appearance of α-SMA and HMGB1 in lung tissue(immunostaining) for the normal (A1, B1), themodel (A2, B2), and 3 g/kg PRM(A3, B3). C,Representative Western blots of α-SMA, FGF-2, PDGF, HMGB1 and RAGE.D, E, Effects of PRM on α-SMA, FGF-2,PDGF, HMGB1 and RAGE expression in BLM-treated lung by Western analysis. Dataare reported as means±SD. PCNA: proliferating cell nuclear antigen.#P<0.01 vs the normal group; *P<0.01vs the model group (one-way ANOVA followed by Dunnett'stest).
Mentions: α-SMA was stained in the cytoplasm, while HMGB1 was stained in the nucleus in thelung tissue, which stained brown for immunohistochemistry, as shown in Figure 6. A smaller amount of α-SMA and HMGB1 wasfound in PRM-treated rats compared to the BLM-treated rats. FGF2, α-SMA, PDGF, HMGB1and RAGE in lung tissue were analyzed by Western blot, as shown in Figure 6. The results showed that FGF2, PDGF,α-SMA, HMGB1 and RAGE were all decreased in the PRM rats. It showed that PRMinhibited the EMT and fibroblast proliferation in vitro andin vivo.

Bottom Line: 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.An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs.PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.

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.

Show MeSH
Related in: MedlinePlus