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Crit Rev Eukaryot Gene Expr. 2019;29(1):69-76. doi: 10.1615/CritRevEukaryotGeneExpr.2019025189.

Calcium-Sensing Receptor Arbitrates Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells via the G Protein-PLC-IP3 Pathway.

Author information

1
Animal Husbandry and Veterinary Institute, Hubei Academy of Agricultural Science, Wuhan, 430064, People's Republic of China; Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture), Wuhan 430070, People's Republic of China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
2
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
3
University College of Veterinary and Animal Sciences, Islamia University of Bahawalpur-63100, Pakistan.
4
Animal Husbandry and Veterinary Institute, Hubei Academy of Agricultural Science, Wuhan, 430064, People's Republic of China; Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture), Wuhan 430070, People's Republic of China.
5
Wuhan General Team of Agricultural Comprehensive Law Enforcement Supervision, Wuhan 430014, People's Republic of China.
6
Department of Clinical Medicine and Surgery, University of Veterinary and Animal Sciences, Lahore-54600, Pakistan.

Abstract

Pulmonary arterial hypertension (PAH), also known as broilers ascites syndrome, is characterized by hypoxia, pulmonary artery pressure, and right heart failure. However, less information is available about the molecular mechanisms of PAH. We evaluated the mediation of calcium-sensing receptor by inducing hypoxia for the possible proliferation of pulmonary artery smooth muscle cells via the G protein pathway. For this purpose, we used an in vitro trial of chicken cell culture and confirmed our results by using immunohistochemistry, immunofluorescence staining, quantitative real-time polymerase chain reaction assay, and Western blotting analysis. Our results showed that the mRNA and protein expression levels of calcium-sensing receptor (CaSR) were significantly upregulated in cells when co-incubated with CaCl2. However, the levels of mRNA and protein were obviously decreased when supplemented with blocking agents (NiCl2, 2-APB, and D609). Furthermore, the experimentally induced hypoxia also upregulated the expression of CaSR gene as compared to CaSR gene expression in control cells. Together, these results indicate that hypoxia plays an important role in the expression of CaSR gene in pulmonary artery smooth muscle cells and reveals new targets for the CaSR excited hypothesis to prevent and control PAH in chickens.

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