Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy
Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mecha...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024033073 |
| _version_ | 1797259742562746368 |
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| author | Ningning Yu Nan Wang Weiqun Zhang Junyu Xue Quan zhou Fengai Hu Xuelian Bai Naiguo Liu |
| author_facet | Ningning Yu Nan Wang Weiqun Zhang Junyu Xue Quan zhou Fengai Hu Xuelian Bai Naiguo Liu |
| author_sort | Ningning Yu |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mechanism is not clear. Ferroptosis is involved in the pathgenesis of many diseases, including IPF. Ferritinophagy is a form of cellular autophagy which regulates intracellular iron homeostasis. The function of DHA on myofibroblasts differentiation of pulmonary and whether related with ferroptosis and ferritinophagy are unknown now. Using human fetal lung fibroblast 1(HFL1) cell line and the qRT-PCR, immunofluorescent and Western blotting techniques, we found that after TGF-β1 treatment, the levels of ɑ-SMA expression and ROS increased; the mRNA and protein levels of FTH1 and NCOA4, the content of Fe2+ and 4-HNE increased significantly at 6h, then gradually reduced with time. After DHA treatment, FHL1 cells appeared ferroptosis; the levels of α-SMA mRNA and protein reduced and the levels of ROS and 4-HNE increased; the Fe2+ levels decreased sharply at 6h, then increased with time, and were higher than normal since 24h; the mRNA and protein levels of FTH1 and NCOA4 decreased, exhibited a downward trend. These results show that Fe2+, ROS and lipid peroxidation are involved in and ferritinophagy is inhibited during fibroblast-to-myofibroblast differentiation; The depletion of Fe2+ at early stage induced by DHA treatment triggers the ferritinophagy in HFL1 cells, leading to degradation of FTH1 and NCOA4 and following increase of Fe2+ levels. DHA may inhibit the fibroblast-to-myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy. |
| first_indexed | 2024-03-07T14:01:29Z |
| format | Article |
| id | doaj.art-d1f8ff3dcc814c9caaee03e4fa4b8497 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:14:16Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d1f8ff3dcc814c9caaee03e4fa4b84972024-03-17T07:57:50ZengElsevierHeliyon2405-84402024-03-01105e27276Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagyNingning Yu0Nan Wang1Weiqun Zhang2Junyu Xue3Quan zhou4Fengai Hu5Xuelian Bai6Naiguo Liu7Medical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaDental Implant Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, PR China; Corresponding author. Medicine Research Center, Binzhou Medical University Hospital, 661 Huanghe Two Road, Binzhou, 256603, PR China.Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mechanism is not clear. Ferroptosis is involved in the pathgenesis of many diseases, including IPF. Ferritinophagy is a form of cellular autophagy which regulates intracellular iron homeostasis. The function of DHA on myofibroblasts differentiation of pulmonary and whether related with ferroptosis and ferritinophagy are unknown now. Using human fetal lung fibroblast 1(HFL1) cell line and the qRT-PCR, immunofluorescent and Western blotting techniques, we found that after TGF-β1 treatment, the levels of ɑ-SMA expression and ROS increased; the mRNA and protein levels of FTH1 and NCOA4, the content of Fe2+ and 4-HNE increased significantly at 6h, then gradually reduced with time. After DHA treatment, FHL1 cells appeared ferroptosis; the levels of α-SMA mRNA and protein reduced and the levels of ROS and 4-HNE increased; the Fe2+ levels decreased sharply at 6h, then increased with time, and were higher than normal since 24h; the mRNA and protein levels of FTH1 and NCOA4 decreased, exhibited a downward trend. These results show that Fe2+, ROS and lipid peroxidation are involved in and ferritinophagy is inhibited during fibroblast-to-myofibroblast differentiation; The depletion of Fe2+ at early stage induced by DHA treatment triggers the ferritinophagy in HFL1 cells, leading to degradation of FTH1 and NCOA4 and following increase of Fe2+ levels. DHA may inhibit the fibroblast-to-myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy.http://www.sciencedirect.com/science/article/pii/S2405844024033073Differentiation of myofibroblastsFerritinophagyFTH1NCOA4Dihydroartemisinin(DHA)Pulmonary fibrosis |
| spellingShingle | Ningning Yu Nan Wang Weiqun Zhang Junyu Xue Quan zhou Fengai Hu Xuelian Bai Naiguo Liu Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy Heliyon Differentiation of myofibroblasts Ferritinophagy FTH1 NCOA4 Dihydroartemisinin(DHA) Pulmonary fibrosis |
| title | Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| title_full | Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| title_fullStr | Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| title_full_unstemmed | Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| title_short | Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| title_sort | dihydroartemisinin dha inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy |
| topic | Differentiation of myofibroblasts Ferritinophagy FTH1 NCOA4 Dihydroartemisinin(DHA) Pulmonary fibrosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024033073 |
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