D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation
Life-threatening chemotherapy-induced thrombocytopenia can increase the risk of bleeding due to a dramatic low platelet count, which may limit or delay treatment schedules in cancer patients. The pressing need for the rapid alleviation of the symptoms of thrombocytopenia has prompted us to search fo...
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| Format: | Article |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00297/full |
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| author | Shilan Ding Shilan Ding Shilan Ding Shilan Ding Min Wang Min Wang Min Wang Min Wang Song Fang Huibo Xu Huiting Fan Yu Tian Yu Tian Yu Tian Yu Tian Yadong Zhai Yadong Zhai Yadong Zhai Yadong Zhai Shan Lu Shan Lu Shan Lu Shan Lu Xin Qi Fei Wei Fei Wei Fei Wei Fei Wei Guibo Sun Guibo Sun Guibo Sun Guibo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun |
| author_facet | Shilan Ding Shilan Ding Shilan Ding Shilan Ding Min Wang Min Wang Min Wang Min Wang Song Fang Huibo Xu Huiting Fan Yu Tian Yu Tian Yu Tian Yu Tian Yadong Zhai Yadong Zhai Yadong Zhai Yadong Zhai Shan Lu Shan Lu Shan Lu Shan Lu Xin Qi Fei Wei Fei Wei Fei Wei Fei Wei Guibo Sun Guibo Sun Guibo Sun Guibo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun |
| author_sort | Shilan Ding |
| collection | DOAJ |
| description | Life-threatening chemotherapy-induced thrombocytopenia can increase the risk of bleeding due to a dramatic low platelet count, which may limit or delay treatment schedules in cancer patients. The pressing need for the rapid alleviation of the symptoms of thrombocytopenia has prompted us to search for novel highly effective and safe thrombopoietic agents. Pharmacological investigations have indicated that dencichine can prevent and treat blood loss and increase the number of platelets. On the basis of the neurotoxicity of dencichine, D-dencichine is artificially synthesized in the laboratory. Our initial results showed that D-dencichine had potential to elevate peripheral platelet levels in mice with carboplatin-induced thrombocytopenia. However, the mechanisms of D-dencichine on thrombopoiesis have been poorly understood. In this study, we found that sequential administration of D-dencichine had a distinct ability to elevate numbers of reticulated platelets, and did not alter their clearance. Moreover, we demonstrated that D-dencichine was able to modulate the return of hematopoietic factors to normal levels, including thrombopoietin and IL-6. However, subsequent analysis revealed that D-dencichine treatment had no direct effects on megakaryocytes proliferation, differentiation, and polyploidization. Further in vitro studies, we demonstrated for the first time that D-dencichine significantly stimulated megakaryocyte adhesion, migration, and proplatelet formation in a dose-dependent manner through extracellular regulated protein kinases1/2 (ERK1/2) and v-akt murine thymoma viral oncogene homolog (AKT) signaling pathways. This study sufficiently characterized the role of the effects of D-dencichine treatment on the regulation of thrombopoiesis and provided a promising avenue for CIT treating. |
| first_indexed | 2024-12-23T11:25:54Z |
| format | Article |
| id | doaj.art-9da4813e3e934a558d08a5e44d504d60 |
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| language | English |
| last_indexed | 2024-12-23T11:25:54Z |
| publishDate | 2018-04-01 |
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| spelling | doaj.art-9da4813e3e934a558d08a5e44d504d602022-12-21T17:48:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-04-01910.3389/fphar.2018.00297320195D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet FormationShilan Ding0Shilan Ding1Shilan Ding2Shilan Ding3Min Wang4Min Wang5Min Wang6Min Wang7Song Fang8Huibo Xu9Huiting Fan10Yu Tian11Yu Tian12Yu Tian13Yu Tian14Yadong Zhai15Yadong Zhai16Yadong Zhai17Yadong Zhai18Shan Lu19Shan Lu20Shan Lu21Shan Lu22Xin Qi23Fei Wei24Fei Wei25Fei Wei26Fei Wei27Guibo Sun28Guibo Sun29Guibo Sun30Guibo Sun31Xiaobo Sun32Xiaobo Sun33Xiaobo Sun34Xiaobo Sun35Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaKunming Shenghuo Pharmaceutical Group Co., Ltd., Kunming, ChinaAcademy of Chinese Medical Sciences of Jilin Province, Jilin, ChinaDepartment of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaDepartment of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, ChinaKey Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, ChinaLife-threatening chemotherapy-induced thrombocytopenia can increase the risk of bleeding due to a dramatic low platelet count, which may limit or delay treatment schedules in cancer patients. The pressing need for the rapid alleviation of the symptoms of thrombocytopenia has prompted us to search for novel highly effective and safe thrombopoietic agents. Pharmacological investigations have indicated that dencichine can prevent and treat blood loss and increase the number of platelets. On the basis of the neurotoxicity of dencichine, D-dencichine is artificially synthesized in the laboratory. Our initial results showed that D-dencichine had potential to elevate peripheral platelet levels in mice with carboplatin-induced thrombocytopenia. However, the mechanisms of D-dencichine on thrombopoiesis have been poorly understood. In this study, we found that sequential administration of D-dencichine had a distinct ability to elevate numbers of reticulated platelets, and did not alter their clearance. Moreover, we demonstrated that D-dencichine was able to modulate the return of hematopoietic factors to normal levels, including thrombopoietin and IL-6. However, subsequent analysis revealed that D-dencichine treatment had no direct effects on megakaryocytes proliferation, differentiation, and polyploidization. Further in vitro studies, we demonstrated for the first time that D-dencichine significantly stimulated megakaryocyte adhesion, migration, and proplatelet formation in a dose-dependent manner through extracellular regulated protein kinases1/2 (ERK1/2) and v-akt murine thymoma viral oncogene homolog (AKT) signaling pathways. This study sufficiently characterized the role of the effects of D-dencichine treatment on the regulation of thrombopoiesis and provided a promising avenue for CIT treating.http://journal.frontiersin.org/article/10.3389/fphar.2018.00297/fullchemotherapy-induced thrombocytopeniathrombopoietinD-dencichineplateletscytokinesmouse |
| spellingShingle | Shilan Ding Shilan Ding Shilan Ding Shilan Ding Min Wang Min Wang Min Wang Min Wang Song Fang Huibo Xu Huiting Fan Yu Tian Yu Tian Yu Tian Yu Tian Yadong Zhai Yadong Zhai Yadong Zhai Yadong Zhai Shan Lu Shan Lu Shan Lu Shan Lu Xin Qi Fei Wei Fei Wei Fei Wei Fei Wei Guibo Sun Guibo Sun Guibo Sun Guibo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation Frontiers in Pharmacology chemotherapy-induced thrombocytopenia thrombopoietin D-dencichine platelets cytokines mouse |
| title | D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation |
| title_full | D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation |
| title_fullStr | D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation |
| title_full_unstemmed | D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation |
| title_short | D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation |
| title_sort | d dencichine regulates thrombopoiesis by promoting megakaryocyte adhesion migration and proplatelet formation |
| topic | chemotherapy-induced thrombocytopenia thrombopoietin D-dencichine platelets cytokines mouse |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00297/full |
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