H-Index
75
Scimago Lab
powered by Scopus
JCR
Clarivate
Analytics
21%
Acceptance
Rate
call: +1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Logo



eISSN: 1643-3750

Get your full text copy in PDF

Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice

Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang

(Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China (mainland))

Med Sci Monit 2017; 23:3932-3941

DOI: 10.12659/MSM.905992


BACKGROUND: The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved.
MATERIAL AND METHODS: The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes were also measured. Regulation of MTA1 on HIF-1α was determined in vitro.
RESULTS: MTA1 deficiency reduced the number of pulmonary alveolar capillaries compared to the wild-type mice. MTA1-KO mice exhibited a decreased expression of HIF-1α and VEGF in the lungs. The retarded growth of the MTA1-KO mice was also noticed during the first week after birth. Accordingly, MTA1 deficiency resulted in increased infant mortality. In surviving adult mice, MTA1 deficiency induced myocardial hypertrophy, highlighted by an increased heart weight/body weight ratio and larger cardiomyocytes. In cultured cells, HIF-1α and VEGF levels were significantly upregulated upon MTA1 overexpression, suggesting a close relationship between all 3 molecules.
CONCLUSIONS: MTA1 participates in the formation of pulmonary capillaries via stabilization of HIF-1α. This finding sheds new light on the function of MTA1 in lung development, opening new avenues for the diagnosis/treatment of related pulmonary diseases.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree