p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension
Aim. Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whethe...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2020/3123968 |
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| author | Chaowei Hu Kun Zuo Kuibao Li Yuanfeng Gao Mulei Chen Roumu Hu Ye Liu Hongjie Chi Hongjiang Wang Yanwen Qin Xiaoyan Liu Jiuchang Zhong Jun Cai Xinchun Yang Jing Li |
| author_facet | Chaowei Hu Kun Zuo Kuibao Li Yuanfeng Gao Mulei Chen Roumu Hu Ye Liu Hongjie Chi Hongjiang Wang Yanwen Qin Xiaoyan Liu Jiuchang Zhong Jun Cai Xinchun Yang Jing Li |
| author_sort | Chaowei Hu |
| collection | DOAJ |
| description | Aim. Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). Methods. We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. Results. In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. Conclusions. Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension. |
| format | Article |
| id | doaj-art-a2acb200e07e4d8281ffa3ea7bee7576 |
| institution | Kabale University |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-a2acb200e07e4d8281ffa3ea7bee75762025-02-03T01:00:19ZengWileyInternational Journal of Hypertension2090-03842090-03922020-01-01202010.1155/2020/31239683123968p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential HypertensionChaowei Hu0Kun Zuo1Kuibao Li2Yuanfeng Gao3Mulei Chen4Roumu Hu5Ye Liu6Hongjie Chi7Hongjiang Wang8Yanwen Qin9Xiaoyan Liu10Jiuchang Zhong11Jun Cai12Xinchun Yang13Jing Li14The Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing an Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaThe Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing an Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaMedical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaHeart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, ChinaAim. Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). Methods. We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. Results. In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. Conclusions. Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.http://dx.doi.org/10.1155/2020/3123968 |
| spellingShingle | Chaowei Hu Kun Zuo Kuibao Li Yuanfeng Gao Mulei Chen Roumu Hu Ye Liu Hongjie Chi Hongjiang Wang Yanwen Qin Xiaoyan Liu Jiuchang Zhong Jun Cai Xinchun Yang Jing Li p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension International Journal of Hypertension |
| title | p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension |
| title_full | p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension |
| title_fullStr | p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension |
| title_full_unstemmed | p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension |
| title_short | p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension |
| title_sort | p38 jnk is required for the proliferation and phenotype changes of vascular smooth muscle cells induced by l3mbtl4 in essential hypertension |
| url | http://dx.doi.org/10.1155/2020/3123968 |
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