Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by chronic inflammation and pathological lung remodeling driven by excessive extracellular matrix deposition. While the flavonol quercetin exhibits established anti-inflammatory and antioxidant properties, its ther...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1594757/full |
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| author | Yuejiao Lan Yuejiao Lan Cuiting Dong Mingda Wu Ruichen Yuan Kunpeng Yang Zhen Yang Yang Chen Jingbin Zhang Bingxue Qi Bingxue Qi Xiaodan Lu Xiaodan Lu |
| author_facet | Yuejiao Lan Yuejiao Lan Cuiting Dong Mingda Wu Ruichen Yuan Kunpeng Yang Zhen Yang Yang Chen Jingbin Zhang Bingxue Qi Bingxue Qi Xiaodan Lu Xiaodan Lu |
| author_sort | Yuejiao Lan |
| collection | DOAJ |
| description | BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by chronic inflammation and pathological lung remodeling driven by excessive extracellular matrix deposition. While the flavonol quercetin exhibits established anti-inflammatory and antioxidant properties, its therapeutic mechanisms against IPF—particularly regarding epithelial-mesenchymal transition (EMT) and inflammation regulation via the follistatin-like 1 (FSTL1)/nuclear factor kappa B (NF-κB) axis—remain incompletely elucidated. This study therefore investigates quercetin’s capacity to mitigate pulmonary fibrosis through targeted modulation of the FSTL1/NF-κB pathway.MethodsA bleomycin (BLM)-induced pulmonary fibrosis mouse model and Transforming Growth Factor Beta 1 (TGF-β1)-induced EMT models in A549 and BEAS-2B cells were employed. The therapeutic effects of quercetin were assessed through H&E, Masson, Sirius red staining, immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of FSTL1 and NF-κB signaling in the anti-fibrotic effects of quercetin was evaluated using FSTL1 knockdown.ResultsIn vivo studies have shown that BLM-induced pulmonary fibrosis and inflammation significantly increased the deposition of extracellular matrix and the levels of interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6), all of which were markedly reduced by quercetin administration. In vitro experiments revealed that quercetin suppressed TGF-β1-induced EMT and inflammation. Importantly, FSTL1 knockdown diminished the anti-inflammatory and anti-EMT effects of quercetin.ConclusionQuercetin exerts its protective effects against pulmonary fibrosis by suppressing FSTL1 expression and modulating the NF-κB signaling pathway, thereby inhibiting both inflammation and EMT process. |
| format | Article |
| id | doaj-art-2d3029ccb66841798acd6fb0b9aad5d4 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-2d3029ccb66841798acd6fb0b9aad5d42025-08-20T03:56:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15947571594757Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosisYuejiao Lan0Yuejiao Lan1Cuiting Dong2Mingda Wu3Ruichen Yuan4Kunpeng Yang5Zhen Yang6Yang Chen7Jingbin Zhang8Bingxue Qi9Bingxue Qi10Xiaodan Lu11Xiaodan Lu12Changchun University of Chinese Medicine, Changchun, Jilin, ChinaJilin Province People’s Hospital, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaJilin Province People’s Hospital, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaJilin Province People’s Hospital, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaJilin Province People’s Hospital, Changchun, Jilin, ChinaChangchun University of Chinese Medicine, Changchun, Jilin, ChinaJilin Province People’s Hospital, Changchun, Jilin, ChinaBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by chronic inflammation and pathological lung remodeling driven by excessive extracellular matrix deposition. While the flavonol quercetin exhibits established anti-inflammatory and antioxidant properties, its therapeutic mechanisms against IPF—particularly regarding epithelial-mesenchymal transition (EMT) and inflammation regulation via the follistatin-like 1 (FSTL1)/nuclear factor kappa B (NF-κB) axis—remain incompletely elucidated. This study therefore investigates quercetin’s capacity to mitigate pulmonary fibrosis through targeted modulation of the FSTL1/NF-κB pathway.MethodsA bleomycin (BLM)-induced pulmonary fibrosis mouse model and Transforming Growth Factor Beta 1 (TGF-β1)-induced EMT models in A549 and BEAS-2B cells were employed. The therapeutic effects of quercetin were assessed through H&E, Masson, Sirius red staining, immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of FSTL1 and NF-κB signaling in the anti-fibrotic effects of quercetin was evaluated using FSTL1 knockdown.ResultsIn vivo studies have shown that BLM-induced pulmonary fibrosis and inflammation significantly increased the deposition of extracellular matrix and the levels of interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6), all of which were markedly reduced by quercetin administration. In vitro experiments revealed that quercetin suppressed TGF-β1-induced EMT and inflammation. Importantly, FSTL1 knockdown diminished the anti-inflammatory and anti-EMT effects of quercetin.ConclusionQuercetin exerts its protective effects against pulmonary fibrosis by suppressing FSTL1 expression and modulating the NF-κB signaling pathway, thereby inhibiting both inflammation and EMT process.https://www.frontiersin.org/articles/10.3389/fphar.2025.1594757/fullpulmonary fibrosisquercetinFSTL1NF-κBEMTinflammation |
| spellingShingle | Yuejiao Lan Yuejiao Lan Cuiting Dong Mingda Wu Ruichen Yuan Kunpeng Yang Zhen Yang Yang Chen Jingbin Zhang Bingxue Qi Bingxue Qi Xiaodan Lu Xiaodan Lu Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis Frontiers in Pharmacology pulmonary fibrosis quercetin FSTL1 NF-κB EMT inflammation |
| title | Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis |
| title_full | Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis |
| title_fullStr | Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis |
| title_full_unstemmed | Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis |
| title_short | Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis |
| title_sort | quercetin ameliorates epithelial mesenchymal transition and inflammation by targeting fstl1 and modulating the nf κb pathway in pulmonary fibrosis |
| topic | pulmonary fibrosis quercetin FSTL1 NF-κB EMT inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1594757/full |
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