YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay
Chronic inflammation is a key pathological process in atherosclerosis. RNA binding proteins (RBPs) have been reported to play an important role in atherosclerotic plaque formation, and they could regulate the expression of inflammatory factors by phosphorylation modification. Y-box binding protein 1...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.945557/full |
| _version_ | 1828428865756725248 |
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| author | Yaqin Tang Zhiwei Li Hongqin Yang Yang Yang Chi Geng Bin Liu Tiantian Zhang Siyang Liu Yunfei Xue Hongkai Zhang Jing Wang Hongmei Zhao |
| author_facet | Yaqin Tang Zhiwei Li Hongqin Yang Yang Yang Chi Geng Bin Liu Tiantian Zhang Siyang Liu Yunfei Xue Hongkai Zhang Jing Wang Hongmei Zhao |
| author_sort | Yaqin Tang |
| collection | DOAJ |
| description | Chronic inflammation is a key pathological process in atherosclerosis. RNA binding proteins (RBPs) have been reported to play an important role in atherosclerotic plaque formation, and they could regulate the expression of inflammatory factors by phosphorylation modification. Y-box binding protein 1 (YB1) is an RBP that has participated in many inflammatory diseases. Here, we found an increased expression of phosphorylated YB1 (pYB1) in atherosclerotic plaques and demonstrated that YB1 dephosphorylation reduced lipid accumulation and lesion area in the aorta in vivo. Additionally, we found that inflammatory cytokines were downregulated in the presence of YB1 dephosphorylation, particularly CCL2, which participates in the pathogenesis of atherosclerosis. Furthermore, we demonstrated that CCL2 mRNA rapid degradation was mediated by the glucocorticoid receptor-mediated mRNA decay (GMD) process during YB1 dephosphorylation, which resulted in the downregulation of CCL2 expression. In conclusion, YB1 phosphorylation affects the development of atherosclerosis through modulating inflammation, and targeting YB1 phosphorylation could be a potential strategy for the treatment of atherosclerosis by anti-inflammation. |
| first_indexed | 2024-12-10T17:24:09Z |
| format | Article |
| id | doaj.art-12a2fe87067d4929bcff8cd7ba7ea999 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-10T17:24:09Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-12a2fe87067d4929bcff8cd7ba7ea9992022-12-22T01:39:53ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.945557945557YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decayYaqin Tang0Zhiwei Li1Hongqin Yang2Yang Yang3Chi Geng4Bin Liu5Tiantian Zhang6Siyang Liu7Yunfei Xue8Hongkai Zhang9Jing Wang10Hongmei Zhao11State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaJilin Zhongtai Biotechnology Co., Ltd, Jilin, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaThe Pathology Department, Beijing Hospital of Traditional Chinese Medicine, The Capital Medical University, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaChronic inflammation is a key pathological process in atherosclerosis. RNA binding proteins (RBPs) have been reported to play an important role in atherosclerotic plaque formation, and they could regulate the expression of inflammatory factors by phosphorylation modification. Y-box binding protein 1 (YB1) is an RBP that has participated in many inflammatory diseases. Here, we found an increased expression of phosphorylated YB1 (pYB1) in atherosclerotic plaques and demonstrated that YB1 dephosphorylation reduced lipid accumulation and lesion area in the aorta in vivo. Additionally, we found that inflammatory cytokines were downregulated in the presence of YB1 dephosphorylation, particularly CCL2, which participates in the pathogenesis of atherosclerosis. Furthermore, we demonstrated that CCL2 mRNA rapid degradation was mediated by the glucocorticoid receptor-mediated mRNA decay (GMD) process during YB1 dephosphorylation, which resulted in the downregulation of CCL2 expression. In conclusion, YB1 phosphorylation affects the development of atherosclerosis through modulating inflammation, and targeting YB1 phosphorylation could be a potential strategy for the treatment of atherosclerosis by anti-inflammation.https://www.frontiersin.org/articles/10.3389/fcvm.2022.945557/fullatherosclerosisRNA binding proteinphosphorylationinflammationmRNA decay |
| spellingShingle | Yaqin Tang Zhiwei Li Hongqin Yang Yang Yang Chi Geng Bin Liu Tiantian Zhang Siyang Liu Yunfei Xue Hongkai Zhang Jing Wang Hongmei Zhao YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay Frontiers in Cardiovascular Medicine atherosclerosis RNA binding protein phosphorylation inflammation mRNA decay |
| title | YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay |
| title_full | YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay |
| title_fullStr | YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay |
| title_full_unstemmed | YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay |
| title_short | YB1 dephosphorylation attenuates atherosclerosis by promoting CCL2 mRNA decay |
| title_sort | yb1 dephosphorylation attenuates atherosclerosis by promoting ccl2 mrna decay |
| topic | atherosclerosis RNA binding protein phosphorylation inflammation mRNA decay |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.945557/full |
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