The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R
Abstract The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells (VSMCs), and one of the main causes of pulmonary hypertension syndrome (PHS) in broilers is pulmonary artery vascular remodeling. Forty Arbor Acres (AA) broilers were rando...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Animal Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s44149-021-00012-w |
| _version_ | 1818918939150778368 |
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| author | Xiaoqi Yang Yang Fu Lianfeng Wu Antong Li Luyao Ji Hao Li Yuxuan Peng Jiabin Zhang Donghai Zhou Huiping Zhou |
| author_facet | Xiaoqi Yang Yang Fu Lianfeng Wu Antong Li Luyao Ji Hao Li Yuxuan Peng Jiabin Zhang Donghai Zhou Huiping Zhou |
| author_sort | Xiaoqi Yang |
| collection | DOAJ |
| description | Abstract The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells (VSMCs), and one of the main causes of pulmonary hypertension syndrome (PHS) in broilers is pulmonary artery vascular remodeling. Forty Arbor Acres (AA) broilers were randomly divided into four groups (n = 10): a control group (deionized water, 0 g/L NaCl), a freshwater group (FW, deionized water + 1 g/L NaCl), highly salinized freshwater group 1 (H-SFW-1, deionized water + 2.5 g/L NaCl) and highly salinized freshwater group 2 (H-SFW-2, deionized water + 5 g/L NaCl). The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water (H-SFW-1 & H-SFW-2), which significantly increased the content of angiotensin II (Ang II) and the expression of angiotensin II type 1 (AT1) receptor protein. Meanwhile, it significantly decreased the expression of dopamine receptor D4 (DRD4) protein. The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers, which could be significantly inhibited by DRD4 agonists (D4A, HY-101384A) and enhanced by DRD4 inhibitors (D4I, HY-B0965). In addition, the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers, either at the transcriptional or translational level. At the same time, the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A. The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner. These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers, accompanied by varying degrees of proliferation of pulmonary artery smooth muscle. This mechanism may involve response of its receptor being induced by increased Ang II, while DRD4 can negatively regulate it. |
| first_indexed | 2024-12-20T00:57:55Z |
| format | Article |
| id | doaj.art-c70077b34df04f518f96ff6c4587359e |
| institution | Directory Open Access Journal |
| issn | 2731-0442 |
| language | English |
| last_indexed | 2024-12-20T00:57:55Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Animal Diseases |
| spelling | doaj.art-c70077b34df04f518f96ff6c4587359e2022-12-21T19:59:04ZengBMCAnimal Diseases2731-04422021-08-011111310.1186/s44149-021-00012-wThe dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1RXiaoqi Yang0Yang Fu1Lianfeng Wu2Antong Li3Luyao Ji4Hao Li5Yuxuan Peng6Jiabin Zhang7Donghai Zhou8Huiping Zhou9Veterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversityVeterinary Clinical Medicine Laboratory, College of Veterinary Medicine, Huazhong Agricultural UniversitySchool of Basic Medical, Hubei University of Science & TechnologyAbstract The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells (VSMCs), and one of the main causes of pulmonary hypertension syndrome (PHS) in broilers is pulmonary artery vascular remodeling. Forty Arbor Acres (AA) broilers were randomly divided into four groups (n = 10): a control group (deionized water, 0 g/L NaCl), a freshwater group (FW, deionized water + 1 g/L NaCl), highly salinized freshwater group 1 (H-SFW-1, deionized water + 2.5 g/L NaCl) and highly salinized freshwater group 2 (H-SFW-2, deionized water + 5 g/L NaCl). The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water (H-SFW-1 & H-SFW-2), which significantly increased the content of angiotensin II (Ang II) and the expression of angiotensin II type 1 (AT1) receptor protein. Meanwhile, it significantly decreased the expression of dopamine receptor D4 (DRD4) protein. The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers, which could be significantly inhibited by DRD4 agonists (D4A, HY-101384A) and enhanced by DRD4 inhibitors (D4I, HY-B0965). In addition, the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers, either at the transcriptional or translational level. At the same time, the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A. The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner. These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers, accompanied by varying degrees of proliferation of pulmonary artery smooth muscle. This mechanism may involve response of its receptor being induced by increased Ang II, while DRD4 can negatively regulate it.https://doi.org/10.1186/s44149-021-00012-wAT1 receptorsDopamine receptor D4PHSVascular smooth muscleAngiotensin II |
| spellingShingle | Xiaoqi Yang Yang Fu Lianfeng Wu Antong Li Luyao Ji Hao Li Yuxuan Peng Jiabin Zhang Donghai Zhou Huiping Zhou The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R Animal Diseases AT1 receptors Dopamine receptor D4 PHS Vascular smooth muscle Angiotensin II |
| title | The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R |
| title_full | The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R |
| title_fullStr | The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R |
| title_full_unstemmed | The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R |
| title_short | The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R |
| title_sort | dopamine receptor d4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating at1r |
| topic | AT1 receptors Dopamine receptor D4 PHS Vascular smooth muscle Angiotensin II |
| url | https://doi.org/10.1186/s44149-021-00012-w |
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