Upregulation of SRF Is Associated With Hypoxic Pulmonary Hypertension by Promoting Viability of Smooth Muscle Cells via Increasing Expression of Bcl-2.
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.
Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Xing
X
Ding
Department of Occupational Medicine, Hefei Third Clinical College Affiliated to Anhui Medical University, Hefei, China.
Sijing
S
Zhou
Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Min
M
Li
Department of Respiratory Medicine, Ningbo First Hospital, Ningbo, China.
Chao
C
Cao
Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Peipei
P
Wu
Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Li
L
Sun
Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Guanghe
G
Fei
Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Ran
0000-0002-3016-1011
R
Wang
D000818:Animals; D015687:Cell Hypoxia; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C000620714:serum response factor, rat; C052617:Bcl2 protein, mouse
Bcl-2; HYPOXIA; PULMONARY HYPERTENSION; SMOOTH MUSCLE CELLS; SRF