Imperatorin ameliorates pulmonary fibrosis via GDF15 expression
Background: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to my...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1292137/full |
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| author | Cheng-Fang Tsai Yen-Chang Chen Ya-Zhen Li Chen-Teng Wu Pei-Chun Chang Wei-Lan Yeh Wei-Lan Yeh |
| author_facet | Cheng-Fang Tsai Yen-Chang Chen Ya-Zhen Li Chen-Teng Wu Pei-Chun Chang Wei-Lan Yeh Wei-Lan Yeh |
| author_sort | Cheng-Fang Tsai |
| collection | DOAJ |
| description | Background: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to myofibroblasts, and accumulation of matrix proteins.Hypothesis/purpose: Imperatorin shows anti-inflammatory effects on alveolar macrophages against acute lung injury. We attempt to evaluate the properties of imperatorin on the basis of fibroblasts.Methods: In in vitro, zymosan was introduced to provoke pro-fibrotic responses in NIH/3T3 or MRC-5 pulmonary fibroblasts. Imperatorin was given for examining its effects against fibrosis. The mice were stimulated by bleomycin, and imperatorin was administered to evaluate the prophylactic potential in vivo.Results: The upregulated expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen protein due to zymosan introduction was decreased by imperatorin in fibroblasts. Zymosan induced the activity of transglutaminase 2 (TGase2) and lysyl oxidase (LOX), which was also inhibited by the administration of imperatorin. Imperatorin alone enhanced sirtuin 1 (SIRT1) activity and growth differentiation factor 15 (GDF15) secretion in fibroblasts via LKB1/AMPK/CREB pathways. In addition, GDF15 exerted a beneficial effect by reducing the protein expression of CTGF, α-SMA, and collagen and the activities of TGase and LOX. Moreover, orally administered imperatorin showed prophylactic effects on bleomycin-induced pulmonary fibrosis in mice.Conclusion: Imperatorin reduces fibrotic marker expression in fibroblasts and also increases GDF15 secretion via the LKB1/AMPK/CREB pathway, attenuating pro-fibrotic responses in vitro. Imperatorin also alleviates pulmonary fibrosis induced by bleomycin in vivo. |
| first_indexed | 2024-03-09T03:08:21Z |
| format | Article |
| id | doaj.art-bb17719baa3247afb27b3a7064ae15e3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-09T03:08:21Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bb17719baa3247afb27b3a7064ae15e32023-12-04T05:28:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-12-011410.3389/fphar.2023.12921371292137Imperatorin ameliorates pulmonary fibrosis via GDF15 expressionCheng-Fang Tsai0Yen-Chang Chen1Ya-Zhen Li2Chen-Teng Wu3Pei-Chun Chang4Wei-Lan Yeh5Wei-Lan Yeh6Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, TaiwanInstitute of New Drug Development, China Medical University, Taichung, TaiwanInstitute of New Drug Development, China Medical University, Taichung, TaiwanDepartment of Surgery, China Medical University Hospital, Taichung, TaiwanDepartment of Bioinformatics and Medical Engineering, Asia University, Taichung, TaiwanInstitute of New Drug Development, China Medical University, Taichung, TaiwanDepartment of Biochemistry, School of Medicine, China Medical University, Taichung, TaiwanBackground: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to myofibroblasts, and accumulation of matrix proteins.Hypothesis/purpose: Imperatorin shows anti-inflammatory effects on alveolar macrophages against acute lung injury. We attempt to evaluate the properties of imperatorin on the basis of fibroblasts.Methods: In in vitro, zymosan was introduced to provoke pro-fibrotic responses in NIH/3T3 or MRC-5 pulmonary fibroblasts. Imperatorin was given for examining its effects against fibrosis. The mice were stimulated by bleomycin, and imperatorin was administered to evaluate the prophylactic potential in vivo.Results: The upregulated expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen protein due to zymosan introduction was decreased by imperatorin in fibroblasts. Zymosan induced the activity of transglutaminase 2 (TGase2) and lysyl oxidase (LOX), which was also inhibited by the administration of imperatorin. Imperatorin alone enhanced sirtuin 1 (SIRT1) activity and growth differentiation factor 15 (GDF15) secretion in fibroblasts via LKB1/AMPK/CREB pathways. In addition, GDF15 exerted a beneficial effect by reducing the protein expression of CTGF, α-SMA, and collagen and the activities of TGase and LOX. Moreover, orally administered imperatorin showed prophylactic effects on bleomycin-induced pulmonary fibrosis in mice.Conclusion: Imperatorin reduces fibrotic marker expression in fibroblasts and also increases GDF15 secretion via the LKB1/AMPK/CREB pathway, attenuating pro-fibrotic responses in vitro. Imperatorin also alleviates pulmonary fibrosis induced by bleomycin in vivo.https://www.frontiersin.org/articles/10.3389/fphar.2023.1292137/fullimperatoringrowth differentiation factor 15fibroblastslungfibrosis |
| spellingShingle | Cheng-Fang Tsai Yen-Chang Chen Ya-Zhen Li Chen-Teng Wu Pei-Chun Chang Wei-Lan Yeh Wei-Lan Yeh Imperatorin ameliorates pulmonary fibrosis via GDF15 expression Frontiers in Pharmacology imperatorin growth differentiation factor 15 fibroblasts lung fibrosis |
| title | Imperatorin ameliorates pulmonary fibrosis via GDF15 expression |
| title_full | Imperatorin ameliorates pulmonary fibrosis via GDF15 expression |
| title_fullStr | Imperatorin ameliorates pulmonary fibrosis via GDF15 expression |
| title_full_unstemmed | Imperatorin ameliorates pulmonary fibrosis via GDF15 expression |
| title_short | Imperatorin ameliorates pulmonary fibrosis via GDF15 expression |
| title_sort | imperatorin ameliorates pulmonary fibrosis via gdf15 expression |
| topic | imperatorin growth differentiation factor 15 fibroblasts lung fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1292137/full |
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