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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 epithelial-mesenchymaltransition (EMT) in A549 cells. A, Representative lightmicroscopic appearance of A549 cells for the normal (A1),transforming growth factor (TGF)-β1-treated (A2), andTGF-β1+0.3 µg/mL PRM (A3). B-D, A549 cellswere incubated with TGF-β1 (5 ng/mL) for 24 h. E-cadherin, vimentin, highmobility group protein B1 (HMGB1), and receptor for advanced glycationend-product (RAGE) expression were analyzed by Western blot. Results arereported as percent increase over the normal. Data are reported as means±SD.PCNA: proliferating cell nuclear antigen. #P<0.01vs the normal group; *P<0.05 vs theTGF-β1 group (one-way ANOVA followed by Dunnett's test).
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f01: Effects of pulmonary rehabilitation mixture (PRM) on epithelial-mesenchymaltransition (EMT) in A549 cells. A, Representative lightmicroscopic appearance of A549 cells for the normal (A1),transforming growth factor (TGF)-β1-treated (A2), andTGF-β1+0.3 µg/mL PRM (A3). B-D, A549 cellswere incubated with TGF-β1 (5 ng/mL) for 24 h. E-cadherin, vimentin, highmobility group protein B1 (HMGB1), and receptor for advanced glycationend-product (RAGE) expression were analyzed by Western blot. Results arereported as percent increase over the normal. Data are reported as means±SD.PCNA: proliferating cell nuclear antigen. #P<0.01vs the normal group; *P<0.05 vs theTGF-β1 group (one-way ANOVA followed by Dunnett's test).

Mentions: As shown in Figure 1A, EMT was significantlyenhanced in A549 cells treated with 5 ng/mL TGF-β1 for 48 h. When theTGF-β1-stimulated cells were exposed to 0.3 μg/mL PRM for 48 h, EMT was attenuated.To investigate how PRM might reduce EMT, its effects on the expression of theepithelial cell marker E-cadherin and the mesenchymal cell marker vimentin wereanalyzed in Western blots. Figure 1B and Cshows that PRM treatment of TGF-β1-stimulated A549 cells attenuated both a decreaseof E-cadherin and an increase of vimentin.


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 epithelial-mesenchymaltransition (EMT) in A549 cells. A, Representative lightmicroscopic appearance of A549 cells for the normal (A1),transforming growth factor (TGF)-β1-treated (A2), andTGF-β1+0.3 µg/mL PRM (A3). B-D, A549 cellswere incubated with TGF-β1 (5 ng/mL) for 24 h. E-cadherin, vimentin, highmobility group protein B1 (HMGB1), and receptor for advanced glycationend-product (RAGE) expression were analyzed by Western blot. Results arereported as percent increase over the normal. Data are reported as means±SD.PCNA: proliferating cell nuclear antigen. #P<0.01vs the normal group; *P<0.05 vs theTGF-β1 group (one-way ANOVA followed by Dunnett's test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f01: Effects of pulmonary rehabilitation mixture (PRM) on epithelial-mesenchymaltransition (EMT) in A549 cells. A, Representative lightmicroscopic appearance of A549 cells for the normal (A1),transforming growth factor (TGF)-β1-treated (A2), andTGF-β1+0.3 µg/mL PRM (A3). B-D, A549 cellswere incubated with TGF-β1 (5 ng/mL) for 24 h. E-cadherin, vimentin, highmobility group protein B1 (HMGB1), and receptor for advanced glycationend-product (RAGE) expression were analyzed by Western blot. Results arereported as percent increase over the normal. Data are reported as means±SD.PCNA: proliferating cell nuclear antigen. #P<0.01vs the normal group; *P<0.05 vs theTGF-β1 group (one-way ANOVA followed by Dunnett's test).
Mentions: As shown in Figure 1A, EMT was significantlyenhanced in A549 cells treated with 5 ng/mL TGF-β1 for 48 h. When theTGF-β1-stimulated cells were exposed to 0.3 μg/mL PRM for 48 h, EMT was attenuated.To investigate how PRM might reduce EMT, its effects on the expression of theepithelial cell marker E-cadherin and the mesenchymal cell marker vimentin wereanalyzed in Western blots. Figure 1B and Cshows that PRM treatment of TGF-β1-stimulated A549 cells attenuated both a decreaseof E-cadherin and an increase of vimentin.

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