Abstract |
Pulmonary hypertension (PH) is a chronic vascular disease characterized by elevated pulmonary arterial resistance and vascular remodeling, and chronic hypoxia plays an important role in PH. Milk fat globule- EGF factor 8 (MFG-E8) is a glycoprotein that regulates cell proliferation and apoptosis, but its role in hypoxia-induced PH is unknown. The current study aimed to determine the function and fundamental mechanisms of MFG-E8 in hypoxia-induced PH. Herein, we exposed mice to hypoxia for 5 weeks, and MFG-E8 was found to be elevated in mouse lung tissues, arteries, and plasma. Compared with wild-type littermates, mice lacking MFG-E8 showed a significant increase in the ratio of pulmonary artery acceleration time to ejection time (PAT/PET), while they showed decreases in right ventricular systolic pressure, the Fulton's Index, percent medial wall thickness (%WT), and vascular muscularization in pulmonary arteries. In addition, MFG-E8 protein levels were also increased in the serum of patients with chronic PH. Similarly, we observed a higher expression of MFG-E8 in human pulmonary artery smooth muscle cells (PASMCs) in the presence of hypoxic stimulation than MFG-E8 in cells in normoxic conditions. Furthermore, MFG-E8 silencing resulted in partial inhibition of proliferation, migration and cell cycle progression in human PASMCs, and the possible mechanisms might involve the interaction between MFG-E8 and the p-Akt/ cyclin D1 pathway. Collectively, our study suggests that the absence of MFG-E8 can attenuate the development of hypoxia-induced PH and vascular remodeling. MFG-E8 can be a potential therapeutic target or a biomarker for PH.
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Authors | Jun Wang, Jixing Wu, Xianying Zhu, Jinkun Chen, Jianping Zhao, Yongjian Xu, Jungang Xie |
Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 236
Issue 1
Pg. 587-600
(01 2021)
ISSN: 1097-4652 [Electronic] United States |
PMID | 32592231
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC. |
Chemical References |
- Antigens, Surface
- Glycoproteins
- MFGE8 protein, human
- Milk Proteins
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Topics |
- Animals
- Antigens, Surface
(genetics)
- Apoptosis
(genetics)
- Cell Proliferation
(genetics)
- Cells, Cultured
- Glycoproteins
(genetics)
- Humans
- Hypertension, Pulmonary
(genetics, pathology)
- Hypoxia
(genetics, pathology)
- Lung
(pathology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Milk Proteins
(genetics)
- Muscle, Smooth, Vascular
(pathology)
- Myocytes, Smooth Muscle
(pathology)
- Pulmonary Artery
(pathology)
- Signal Transduction
(genetics)
- Vascular Remodeling
(genetics)
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