Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway
Introduction: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic dr...
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Elsevier
2025-02-01
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| Series: | Journal of Advanced Research |
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| author | Tingting Zhang Mengmeng Zhu Jialing Ma Zhenghong Liu Zhidan Zhang Meijie Chen Yaping Zhao Huaxin Li Shengnan Wang Xiaoning Wei Wenwen Zhang Xiaoxiao Yang Peter J. Little Danielle Kamato Hao Hu Yajun Duan Baotong Zhang Jianbo Xiao Suowen Xu Yuanli Chen |
| author_facet | Tingting Zhang Mengmeng Zhu Jialing Ma Zhenghong Liu Zhidan Zhang Meijie Chen Yaping Zhao Huaxin Li Shengnan Wang Xiaoning Wei Wenwen Zhang Xiaoxiao Yang Peter J. Little Danielle Kamato Hao Hu Yajun Duan Baotong Zhang Jianbo Xiao Suowen Xu Yuanli Chen |
| author_sort | Tingting Zhang |
| collection | DOAJ |
| description | Introduction: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. Objectives: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. Methods: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. Results: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/β-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/β-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. Conclusion: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/β-catenin signalling pathways. |
| format | Article |
| id | doaj-art-8b9cfa37edee4a7fa55bb5b494d4d6cd |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj-art-8b9cfa37edee4a7fa55bb5b494d4d6cd2025-01-18T05:04:20ZengElsevierJournal of Advanced Research2090-12322025-02-0168445457Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathwayTingting Zhang0Mengmeng Zhu1Jialing Ma2Zhenghong Liu3Zhidan Zhang4Meijie Chen5Yaping Zhao6Huaxin Li7Shengnan Wang8Xiaoning Wei9Wenwen Zhang10Xiaoxiao Yang11Peter J. Little12Danielle Kamato13Hao Hu14Yajun Duan15Baotong Zhang16Jianbo Xiao17Suowen Xu18Yuanli Chen19Key Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaDepartment of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaTianjin Central Hospital of Obstetrics and Gynecology, Tianjin, ChinaKey Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, ChinaSchool of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, AustraliaDiscovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, AustraliaDepartment of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Analytical and Food Chemistry, Faculty of Sciences, Universidade de Vigo, Nutrition and Bromatology Group, Ourense, SpainDepartment of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Corresponding authors.Key Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China; Corresponding authors.Introduction: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. Objectives: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. Methods: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. Results: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/β-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/β-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. Conclusion: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/β-catenin signalling pathways.http://www.sciencedirect.com/science/article/pii/S2090123224000821Vascular calcificationMoscatilinDendrophenolWNT3β-cateninIL13RΑ2 |
| spellingShingle | Tingting Zhang Mengmeng Zhu Jialing Ma Zhenghong Liu Zhidan Zhang Meijie Chen Yaping Zhao Huaxin Li Shengnan Wang Xiaoning Wei Wenwen Zhang Xiaoxiao Yang Peter J. Little Danielle Kamato Hao Hu Yajun Duan Baotong Zhang Jianbo Xiao Suowen Xu Yuanli Chen Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway Journal of Advanced Research Vascular calcification Moscatilin Dendrophenol WNT3 β-catenin IL13RΑ2 |
| title | Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway |
| title_full | Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway |
| title_fullStr | Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway |
| title_full_unstemmed | Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway |
| title_short | Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway |
| title_sort | moscatilin inhibits vascular calcification by activating il13ra2 dependent inhibition of stat3 and attenuating the wnt3 β catenin signalling pathway |
| topic | Vascular calcification Moscatilin Dendrophenol WNT3 β-catenin IL13RΑ2 |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000821 |
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