Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling
Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the...
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01427/full |
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| author | Hu-Qiang He Hu-Qiang He Hu-Qiang He Betty Yuen Kwan Law Betty Yuen Kwan Law Ni Zhang Ni Zhang Cong-ling Qiu Cong-ling Qiu Yuan-Qing Qu Yuan-Qing Qu An-Guo Wu An-Guo Wu Yu Han Yu Han Qi Song Qi Song Qi Song Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Yong Liu Yan-Zheng He Vincent Kam Wai Wong Vincent Kam Wai Wong |
| author_facet | Hu-Qiang He Hu-Qiang He Hu-Qiang He Betty Yuen Kwan Law Betty Yuen Kwan Law Ni Zhang Ni Zhang Cong-ling Qiu Cong-ling Qiu Yuan-Qing Qu Yuan-Qing Qu An-Guo Wu An-Guo Wu Yu Han Yu Han Qi Song Qi Song Qi Song Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Yong Liu Yan-Zheng He Vincent Kam Wai Wong Vincent Kam Wai Wong |
| author_sort | Hu-Qiang He |
| collection | DOAJ |
| description | Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds from traditional Chinese medicines (TCM) that exhibit an anti-arteriosclerosis effect. In β-glycerophosphate (β-GP)-stimulated human aortic smooth muscle cells (HASMCs), the calcium level was increased and the expression of the calcification-related proteins OPG, OPN, Runx2, and BMP2 were all up-regulated, followed by autophagy induction and apoptosis. Meanwhile, we further revealed that β-GP induced apoptosis of human osteoblasts and promoted differentiation of osteoblasts through Wnt/β-catenin signaling. Bavachin, a natural compound from Psoralea corylifolia, dose-dependently reduced the level of intracellular calcium and the expression of calcification-related proteins OPG, OPN, Runx2 and BMP2, thus inhibiting cell apoptosis. In addition, bavachin increased LC3-II and beclin1 expression, along with intracellular LC3-II puncta formation, which autophagy induction is Atg7-dependent and is regulated by suppression of mTOR signaling. Furthermore, addition of autophagy inhibitor, wortmannin (WM) attenuated the inhibitory effect of bavachin on β-GP-induced calcification and apoptosis in HASMCs. Collectively, the present study revealed that bavachin protects HASMCs against apoptosis and calcification by activation of the Atg7/mTOR-autophagy pathway and suppression of the β-catenin signaling, our findings provide a potential clinical application for bavachin in the therapy of cardiovascular disease. |
| first_indexed | 2024-12-21T17:03:30Z |
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| last_indexed | 2024-12-21T17:03:30Z |
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| spelling | doaj.art-cf0499e2515f42ce8137877d7275d5362022-12-21T18:56:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-12-011010.3389/fphar.2019.01427458180Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin SignalingHu-Qiang He0Hu-Qiang He1Hu-Qiang He2Betty Yuen Kwan Law3Betty Yuen Kwan Law4Ni Zhang5Ni Zhang6Cong-ling Qiu7Cong-ling Qiu8Yuan-Qing Qu9Yuan-Qing Qu10An-Guo Wu11An-Guo Wu12Yu Han13Yu Han14Qi Song15Qi Song16Qi Song17Wen-Lu Zheng18Wen-Lu Zheng19Wen-Lu Zheng20Wen-Lu Zheng21Yong Liu22Yan-Zheng He23Vincent Kam Wai Wong24Vincent Kam Wai Wong25Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Vascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Thoracic and Cardial Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaNuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaLaboratory of Chinese Materia Medical, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaInstitute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Southwest Medical University, Luzhou, ChinaDepartment of Vascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Vascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaVascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds from traditional Chinese medicines (TCM) that exhibit an anti-arteriosclerosis effect. In β-glycerophosphate (β-GP)-stimulated human aortic smooth muscle cells (HASMCs), the calcium level was increased and the expression of the calcification-related proteins OPG, OPN, Runx2, and BMP2 were all up-regulated, followed by autophagy induction and apoptosis. Meanwhile, we further revealed that β-GP induced apoptosis of human osteoblasts and promoted differentiation of osteoblasts through Wnt/β-catenin signaling. Bavachin, a natural compound from Psoralea corylifolia, dose-dependently reduced the level of intracellular calcium and the expression of calcification-related proteins OPG, OPN, Runx2 and BMP2, thus inhibiting cell apoptosis. In addition, bavachin increased LC3-II and beclin1 expression, along with intracellular LC3-II puncta formation, which autophagy induction is Atg7-dependent and is regulated by suppression of mTOR signaling. Furthermore, addition of autophagy inhibitor, wortmannin (WM) attenuated the inhibitory effect of bavachin on β-GP-induced calcification and apoptosis in HASMCs. Collectively, the present study revealed that bavachin protects HASMCs against apoptosis and calcification by activation of the Atg7/mTOR-autophagy pathway and suppression of the β-catenin signaling, our findings provide a potential clinical application for bavachin in the therapy of cardiovascular disease.https://www.frontiersin.org/article/10.3389/fphar.2019.01427/fullvascular calcificationautophagyWnt/β-cateninApoptosisAtg7 |
| spellingShingle | Hu-Qiang He Hu-Qiang He Hu-Qiang He Betty Yuen Kwan Law Betty Yuen Kwan Law Ni Zhang Ni Zhang Cong-ling Qiu Cong-ling Qiu Yuan-Qing Qu Yuan-Qing Qu An-Guo Wu An-Guo Wu Yu Han Yu Han Qi Song Qi Song Qi Song Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Wen-Lu Zheng Yong Liu Yan-Zheng He Vincent Kam Wai Wong Vincent Kam Wai Wong Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling Frontiers in Pharmacology vascular calcification autophagy Wnt/β-catenin Apoptosis Atg7 |
| title | Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling |
| title_full | Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling |
| title_fullStr | Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling |
| title_full_unstemmed | Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling |
| title_short | Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling |
| title_sort | bavachin protects human aortic smooth muscle cells against β glycerophosphate mediated vascular calcification and apoptosis via activation of mtor dependent autophagy and suppression of β catenin signaling |
| topic | vascular calcification autophagy Wnt/β-catenin Apoptosis Atg7 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01427/full |
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