TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling
Pulmonary fibrosis is highly lethal with limited treatments. Butaselen (BS) is an inhibitor of thioredoxin reductase (TrxR)/thioredoxin (Trx) with anti-tumor activity. However, its impact on pulmonary fibrosis and the involved mechanisms remain unclear. Here, we demonstrate that BS is a potential dr...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223016207 |
| _version_ | 1797404587849678848 |
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| author | Yifan Chen Hanwei Yin Jing Sun Guozhou Zhang Ying Zhang Huihui Zeng |
| author_facet | Yifan Chen Hanwei Yin Jing Sun Guozhou Zhang Ying Zhang Huihui Zeng |
| author_sort | Yifan Chen |
| collection | DOAJ |
| description | Pulmonary fibrosis is highly lethal with limited treatments. Butaselen (BS) is an inhibitor of thioredoxin reductase (TrxR)/thioredoxin (Trx) with anti-tumor activity. However, its impact on pulmonary fibrosis and the involved mechanisms remain unclear. Here, we demonstrate that BS is a potential drug for the treatment of pulmonary fibrosis. Specifically, BS can inhibit pulmonary fibrosis both in vitro and in vivo, with comparable efficacy and enhanced safety when compared with pirfenidone. BS and dexamethasone display a synergistic effect in inhibiting pulmonary fibrosis both in vitro and in vivo. Mechanistic studies reveal that BS can inhibit the TrxR activity during pulmonary fibrosis. RNA-sequencing analysis identifies that genes of ECM-related signaling pathways are notably affected by BS. BS can not only inhibit the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduce pulmonary fibrosis-related inflammation, but also reduce NF-κB-activated transcriptional expression of transforming growth factor-β1 (TGF-β1), which leads to the inactivation of Smad2/Smad3 and decrease of collagen formation and fibrosis. Moreover, the knockdown of Trx1 with siRNA can also inhibit NF-κB/TGF-β1/Smads signaling. In conclusion, the TrxR/Trx inhibitor butaselen can suppress pulmonary fibrosis by inhibiting NF-κB/TGF-β1/Smads signaling. |
| first_indexed | 2024-03-09T02:57:11Z |
| format | Article |
| id | doaj.art-91b88e05646b42f6a3a30b48c1c16596 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:57:11Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-91b88e05646b42f6a3a30b48c1c165962023-12-05T04:14:29ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115822TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signalingYifan Chen0Hanwei Yin1Jing Sun2Guozhou Zhang3Ying Zhang4Huihui Zeng5State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China; Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China; Cancer Center, Peking University Third Hospital, Beijing, China; Biobank, Peking University Third Hospital, Beijing, ChinaShanghai Yuanxi Medicine Corp, Shanghai, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaShanghai Yuanxi Medicine Corp, Shanghai, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China; Corresponding author.Pulmonary fibrosis is highly lethal with limited treatments. Butaselen (BS) is an inhibitor of thioredoxin reductase (TrxR)/thioredoxin (Trx) with anti-tumor activity. However, its impact on pulmonary fibrosis and the involved mechanisms remain unclear. Here, we demonstrate that BS is a potential drug for the treatment of pulmonary fibrosis. Specifically, BS can inhibit pulmonary fibrosis both in vitro and in vivo, with comparable efficacy and enhanced safety when compared with pirfenidone. BS and dexamethasone display a synergistic effect in inhibiting pulmonary fibrosis both in vitro and in vivo. Mechanistic studies reveal that BS can inhibit the TrxR activity during pulmonary fibrosis. RNA-sequencing analysis identifies that genes of ECM-related signaling pathways are notably affected by BS. BS can not only inhibit the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduce pulmonary fibrosis-related inflammation, but also reduce NF-κB-activated transcriptional expression of transforming growth factor-β1 (TGF-β1), which leads to the inactivation of Smad2/Smad3 and decrease of collagen formation and fibrosis. Moreover, the knockdown of Trx1 with siRNA can also inhibit NF-κB/TGF-β1/Smads signaling. In conclusion, the TrxR/Trx inhibitor butaselen can suppress pulmonary fibrosis by inhibiting NF-κB/TGF-β1/Smads signaling.http://www.sciencedirect.com/science/article/pii/S0753332223016207Pulmonary fibrosisThioredoxin reductaseThioredoxinNuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)Transforming growth factor-β1 (TGF-β1) |
| spellingShingle | Yifan Chen Hanwei Yin Jing Sun Guozhou Zhang Ying Zhang Huihui Zeng TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling Biomedicine & Pharmacotherapy Pulmonary fibrosis Thioredoxin reductase Thioredoxin Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) Transforming growth factor-β1 (TGF-β1) |
| title | TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling |
| title_full | TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling |
| title_fullStr | TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling |
| title_full_unstemmed | TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling |
| title_short | TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling |
| title_sort | trxr trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing nf κb tgf β1 smads signaling |
| topic | Pulmonary fibrosis Thioredoxin reductase Thioredoxin Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) Transforming growth factor-β1 (TGF-β1) |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223016207 |
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