Jiawei Maxing Shigan Tang alleviates radiation-induced lung injury via TGF-β1/Smad signaling pathway mediated by regulatory T cells
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
ETHNOPHARMACOLOGICAL RELEVANCE: Radiation-induced lung injury (RILI) is a common complication during thoracic radiotherapy which impairs the quality of life in patients and limits radiation doses. Jiawei Maxing Shigan Tang (JMST), which is a modified decoction made of Ephedra, Apricot Kernel, Gypsum, and Licorice, can alleviate the symptoms of RILI in patients. Previous studies and preliminary findings suggested a potential molecular mechanism of JMST in the treatment of RILI. Further studies are needed.
AIM OF THE STUDY: To elucidate the mechanisms of how regulatory T cells (Tregs) promote RILI and the effect of JMST on Tregs, as well as the corresponding pathway.
MATERIALS AND METHODS: CD4+CD25+ Tregs were isolated from rats, and the supernatant's TGF-β1 level was examined by using enzyme-linked immunosorbent assay (ELISA). Type II alveolar epithelial cells (AECs) were co-cultured with the supernatant of Tregs, and the expression levels of epithelial-to-mesenchymal transition (EMT)-related and TGF-β1/Smad signaling pathway-related proteins were analyzed by using western blotting (WB). Afterward, the Tregs were incubated with different concentrations of JMST. The cell viability and TGF-β1 concentration were confirmed by cell counting kit-8 (CCK-8) assay and ELISA, respectively. The optimized concentration of JMST was applied in vitro and vivo experiments. The specific mechanism was investigated through the combination of using flow cytometry, lung histopathology analysis, ELISA, and WB.
RESULTS: Radiation could promote Tregs to secrete TGF-β1. After radiation, the expression levels of Smad2/3, phosphorylated Smad2/3 (p-Smad2/3), Smad4 and mesenchymal markers Vimentin and α-SMA were all increased, while the expression level of epithelial markers E-cadherin was decreased. The expression levels of these proteins were reversed after interventions involving Treg cell activation inhibition or TGF-β1 receptor inhibitor. JMST reduced the number of Tregs in lung tissue and alleviated the degree of pulmonary fibrosis. The expression of Smad2/3, p-Smad2/3, Smad4, TGF-β1, Vimentin, and α-SMA were significantly downregulated, while the E-cadherin was upregulated, through the intervention of JMST.
CONCLUSION: Tregs could mediate EMT through TGF-β1/Smad pathway. JMST inhibits EMT via TGF-β1/Smad pathway by regulating Tregs, therefore alleviating RILI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:320 |
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| Enthalten in: |
Journal of ethnopharmacology - 320(2023) vom: 10. Feb., Seite 117389 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Menglei [VerfasserIn] |
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| Links: |
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| Themen: |
Cadherins |
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| Anmerkungen: |
Date Completed 06.12.2023 Date Revised 06.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jep.2023.117389 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364365897 |
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| 500 | |a Date Completed 06.12.2023 | ||
| 500 | |a Date Revised 06.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a ETHNOPHARMACOLOGICAL RELEVANCE: Radiation-induced lung injury (RILI) is a common complication during thoracic radiotherapy which impairs the quality of life in patients and limits radiation doses. Jiawei Maxing Shigan Tang (JMST), which is a modified decoction made of Ephedra, Apricot Kernel, Gypsum, and Licorice, can alleviate the symptoms of RILI in patients. Previous studies and preliminary findings suggested a potential molecular mechanism of JMST in the treatment of RILI. Further studies are needed | ||
| 520 | |a AIM OF THE STUDY: To elucidate the mechanisms of how regulatory T cells (Tregs) promote RILI and the effect of JMST on Tregs, as well as the corresponding pathway | ||
| 520 | |a MATERIALS AND METHODS: CD4+CD25+ Tregs were isolated from rats, and the supernatant's TGF-β1 level was examined by using enzyme-linked immunosorbent assay (ELISA). Type II alveolar epithelial cells (AECs) were co-cultured with the supernatant of Tregs, and the expression levels of epithelial-to-mesenchymal transition (EMT)-related and TGF-β1/Smad signaling pathway-related proteins were analyzed by using western blotting (WB). Afterward, the Tregs were incubated with different concentrations of JMST. The cell viability and TGF-β1 concentration were confirmed by cell counting kit-8 (CCK-8) assay and ELISA, respectively. The optimized concentration of JMST was applied in vitro and vivo experiments. The specific mechanism was investigated through the combination of using flow cytometry, lung histopathology analysis, ELISA, and WB | ||
| 520 | |a RESULTS: Radiation could promote Tregs to secrete TGF-β1. After radiation, the expression levels of Smad2/3, phosphorylated Smad2/3 (p-Smad2/3), Smad4 and mesenchymal markers Vimentin and α-SMA were all increased, while the expression level of epithelial markers E-cadherin was decreased. The expression levels of these proteins were reversed after interventions involving Treg cell activation inhibition or TGF-β1 receptor inhibitor. JMST reduced the number of Tregs in lung tissue and alleviated the degree of pulmonary fibrosis. The expression of Smad2/3, p-Smad2/3, Smad4, TGF-β1, Vimentin, and α-SMA were significantly downregulated, while the E-cadherin was upregulated, through the intervention of JMST | ||
| 520 | |a CONCLUSION: Tregs could mediate EMT through TGF-β1/Smad pathway. JMST inhibits EMT via TGF-β1/Smad pathway by regulating Tregs, therefore alleviating RILI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Epithelial-to-mesenchymal transition | |
| 650 | 4 | |a Jiawei Maxing Shigan Tang | |
| 650 | 4 | |a Pulmonary fibrosis | |
| 650 | 4 | |a Radiation-induced lung injury | |
| 650 | 4 | |a Regulatory T cells | |
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| 650 | 7 | |a Vimentin |2 NLM | |
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| 700 | 1 | |a Zhang, Pengcheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Kezhan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Jingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Yazhen |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xuefei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Shengyou |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jinhua |e verfasserin |4 aut | |
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