Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway
In recent study, the pathological mechanism of liver fibrosis has been associated with hepatic stellate cell (HSC) senescence. Targeted induction of HSC senescence is considered as a new strategy to remove activated HSC. Nevertheless, little is known about the role of ferritinophagy in cell senescen...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223004419 |
| _version_ | 1797837159280934912 |
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| author | Ying Sun Jingdan Weng Xiaolei Chen Shuyao Ma Yuxin Zhang Feng Zhang Zili Zhang Feixia Wang Jiangjuan Shao Shizhong Zheng |
| author_facet | Ying Sun Jingdan Weng Xiaolei Chen Shuyao Ma Yuxin Zhang Feng Zhang Zili Zhang Feixia Wang Jiangjuan Shao Shizhong Zheng |
| author_sort | Ying Sun |
| collection | DOAJ |
| description | In recent study, the pathological mechanism of liver fibrosis has been associated with hepatic stellate cell (HSC) senescence. Targeted induction of HSC senescence is considered as a new strategy to remove activated HSC. Nevertheless, little is known about the role of ferritinophagy in cell senescence. In this study, we reported that Oroxylin A from Scutellaria baicalensis Georgi can regulate HSC senescence induced by ferritinophagy through the cGAS-STING pathway to reduce liver fibrosis. We first found that Oroxylin A treatment alleviated the pathological changes of liver fibrosis, reduced collagen deposition, and significantly inhibited liver fibrosis. Interestingly, Oroxylin A treatment can activate HSC ferritinophagy and further induce HSC senescence. It is noteworthy that ferritinophagy is mediated by nuclear receptor coactivator 4 (NCOA4), an important selective mediator for ferritin degradation. NCOA4 siRNA causes Oroxylin A to reduce the degree of telomerase activity in HSCs and induce the expression of senescence markers, such as SA-β-Gal and related marker proteins. Importantly, the cGAS-STING pathway is crucial to the activation of HSC ferritinophagy by Oroxylin A. Specifically, Oroxylin A can promote the secretion of cytokines like IFN-β by the cGAS-STING pathway to regulate ferritinophagy. cGAS siRNA resulted in a dose-dependent decrease in the expression of NCOA4, a significant reduction in the expression level of autophagy-related phenotype, and a decrease in the content of ROS and iron ions in HSCs. In conclusion, we identified the new role of ferritinophagy and the GAS-STING pathway in Oroxylin A -mediated anti-hepatic fibrosis. |
| first_indexed | 2024-04-09T15:20:19Z |
| format | Article |
| id | doaj.art-5b13d53729834b308752402783338f2e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:20:19Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-5b13d53729834b308752402783338f2e2023-04-29T14:46:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114653Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathwayYing Sun0Jingdan Weng1Xiaolei Chen2Shuyao Ma3Yuxin Zhang4Feng Zhang5Zili Zhang6Feixia Wang7Jiangjuan Shao8Shizhong Zheng9Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaCorresponding authors.; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaCorresponding authors.; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, ChinaIn recent study, the pathological mechanism of liver fibrosis has been associated with hepatic stellate cell (HSC) senescence. Targeted induction of HSC senescence is considered as a new strategy to remove activated HSC. Nevertheless, little is known about the role of ferritinophagy in cell senescence. In this study, we reported that Oroxylin A from Scutellaria baicalensis Georgi can regulate HSC senescence induced by ferritinophagy through the cGAS-STING pathway to reduce liver fibrosis. We first found that Oroxylin A treatment alleviated the pathological changes of liver fibrosis, reduced collagen deposition, and significantly inhibited liver fibrosis. Interestingly, Oroxylin A treatment can activate HSC ferritinophagy and further induce HSC senescence. It is noteworthy that ferritinophagy is mediated by nuclear receptor coactivator 4 (NCOA4), an important selective mediator for ferritin degradation. NCOA4 siRNA causes Oroxylin A to reduce the degree of telomerase activity in HSCs and induce the expression of senescence markers, such as SA-β-Gal and related marker proteins. Importantly, the cGAS-STING pathway is crucial to the activation of HSC ferritinophagy by Oroxylin A. Specifically, Oroxylin A can promote the secretion of cytokines like IFN-β by the cGAS-STING pathway to regulate ferritinophagy. cGAS siRNA resulted in a dose-dependent decrease in the expression of NCOA4, a significant reduction in the expression level of autophagy-related phenotype, and a decrease in the content of ROS and iron ions in HSCs. In conclusion, we identified the new role of ferritinophagy and the GAS-STING pathway in Oroxylin A -mediated anti-hepatic fibrosis.http://www.sciencedirect.com/science/article/pii/S0753332223004419Liver fibrosisOroxylin ACell senescenceFerritinophagycGAS-STING pathway |
| spellingShingle | Ying Sun Jingdan Weng Xiaolei Chen Shuyao Ma Yuxin Zhang Feng Zhang Zili Zhang Feixia Wang Jiangjuan Shao Shizhong Zheng Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway Biomedicine & Pharmacotherapy Liver fibrosis Oroxylin A Cell senescence Ferritinophagy cGAS-STING pathway |
| title | Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway |
| title_full | Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway |
| title_fullStr | Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway |
| title_full_unstemmed | Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway |
| title_short | Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway |
| title_sort | oroxylin a activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cgas sting pathway |
| topic | Liver fibrosis Oroxylin A Cell senescence Ferritinophagy cGAS-STING pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223004419 |
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