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Upregulation of SRF Is Associated With Hypoxic Pulmonary Hypertension by Promoting Viability of Smooth Muscle Cells via Increasing Expression of Bcl‐2
Author(s) -
Ding Xing,
Zhou Sijing,
Li Min,
Cao Chao,
Wu Peipei,
Sun Li,
Fei Guanghe,
Wang Ran
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25922
Subject(s) - hypoxia (environmental) , western blot , downregulation and upregulation , pulmonary hypertension , apoptosis , immunohistochemistry , pulmonary artery , blot , viability assay , serum response factor , chemistry , microbiology and biotechnology , andrology , medicine , pathology , biology , transcription factor , biochemistry , organic chemistry , oxygen , gene
ABSTRACT The aim of study was to investigate the involvement of hypoxia‐induced upregulation of serum response factor (SRF) and its downstream effector, B cell leukemia‐2 (Bcl‐2), in hypoxia‐induced pulmonary hypertension (PH). Immunohistochemistry analysis and western blot analysis were used to detect the levels of SRF and Bcl‐2 in rats exposed to hypoxia. Furthermore, the regulatory relationship between SRF and Bcl‐2 was investigated in PASMCs using real‐time PCR and western‐blot analysis. We found that mPAP (mean pulmonary arterial pressure) and WA (the ratio of vascular wall area to external diameter) were increased after exposure to hypoxia, while LA (the ratio of vascular lumen area to total area) decreased after exposure to hypoxia. The immunohistochemistry analysis displayed a substantial increase in SRF and Bcl‐2 in pulmonary arterial walls after 14 days of hypoxia. And the western blotting showed that SRF and Bcl‐2 protein levels were much higher after 7 days of hypoxia and then remained at a high level. And then the levels of SRF and Bcl‐2 in pulmonary artery smooth muscle cells (PASMCs) exposed to hypoxia were substantially suppressed following introduction of SRF siRNA, and the level of Bcl‐2 was remarkably inhibited by Bcl‐2 siRNA, while Bcl‐2 siRNA had no effect on SRF level. Finally, SRF siRNA, and Bcl‐2 siRNA significantly reduced viability of PASMCs exposed to hypoxia, and enhanced apoptosis of PASMCs exposed to hypoxia. These data validated that SRF responded to hypoxia, which subsequently was involved in pulmonary hypertension by abnormally promoting viability of PASMCs via modulating expression of Bcl‐2. J. Cell. Biochem. 118: 2731–2738, 2017. © 2017 Wiley Periodicals, Inc.