Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway
Activation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The present study aims to address this issue. We d...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1016/j.fob.2015.08.007 |
| _version_ | 1811299537990451200 |
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| author | Yang Song Yonghong Zhang Haoxiang Jiang Yanting Zhu Lu Liu Wei Feng Lan Yang Yibin Wang Manxiang Li |
| author_facet | Yang Song Yonghong Zhang Haoxiang Jiang Yanting Zhu Lu Liu Wei Feng Lan Yang Yibin Wang Manxiang Li |
| author_sort | Yang Song |
| collection | DOAJ |
| description | Activation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The present study aims to address this issue. We demonstrated that over‐expression of intracellular domain of the Notch3 receptor (NICD3) by adenovirus transfection dramatically induced proliferation of primary cultured pulmonary artery smooth muscle cells. This was accompanied with up‐regulation of Hes1 protein and down‐regulation of p27Kip1 protein. More importantly, we observed that prior silencing of Hes1 with siRNA blocked NICD3 over‐expression‐induced p27Kip1 reduction and cell proliferation. The present study suggests that Hes1 lies downstream of NICD3 and particularly mediates Notch3 signaling‐induced proliferation of pulmonary arterial smooth muscle cells by down‐regulation of p27Kip1 expression. |
| first_indexed | 2024-04-13T06:37:20Z |
| format | Article |
| id | doaj.art-3fad6e1110c8461c91a84c9162fbfc39 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-13T06:37:20Z |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-3fad6e1110c8461c91a84c9162fbfc392022-12-22T02:57:50ZengWileyFEBS Open Bio2211-54632015-01-015165666010.1016/j.fob.2015.08.007Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathwayYang Song0Yonghong Zhang1Haoxiang Jiang2Yanting Zhu3Lu Liu4Wei Feng5Lan Yang6Yibin Wang7Manxiang Li8Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartment of Radiology, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, PR ChinaDepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaDepartments of Anesthesiology, Physiology, and Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USADepartment of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR ChinaActivation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The present study aims to address this issue. We demonstrated that over‐expression of intracellular domain of the Notch3 receptor (NICD3) by adenovirus transfection dramatically induced proliferation of primary cultured pulmonary artery smooth muscle cells. This was accompanied with up‐regulation of Hes1 protein and down‐regulation of p27Kip1 protein. More importantly, we observed that prior silencing of Hes1 with siRNA blocked NICD3 over‐expression‐induced p27Kip1 reduction and cell proliferation. The present study suggests that Hes1 lies downstream of NICD3 and particularly mediates Notch3 signaling‐induced proliferation of pulmonary arterial smooth muscle cells by down‐regulation of p27Kip1 expression.https://doi.org/10.1016/j.fob.2015.08.007PASMCsProliferationNICD3Hes1P27Kip1 |
| spellingShingle | Yang Song Yonghong Zhang Haoxiang Jiang Yanting Zhu Lu Liu Wei Feng Lan Yang Yibin Wang Manxiang Li Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway FEBS Open Bio PASMCs Proliferation NICD3 Hes1 P27Kip1 |
| title | Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway |
| title_full | Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway |
| title_fullStr | Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway |
| title_full_unstemmed | Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway |
| title_short | Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway |
| title_sort | activation of notch3 promotes pulmonary arterial smooth muscle cells proliferation via hes1 p27kip1 signaling pathway |
| topic | PASMCs Proliferation NICD3 Hes1 P27Kip1 |
| url | https://doi.org/10.1016/j.fob.2015.08.007 |
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