rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3 η and CA1/Kininogen Signal Transduction

Wan-Cheng Yu; Hai-Ying Chen; Hong-Li Yang; Peng Xia; Cheng-Wei Zou; Tong-Wen Sun; Le-Xin Wang

doi:10.1155/2019/6768571

rBMSC/Cav-1^F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3 η and CA1/Kininogen Signal Transduction

Stem Cells Int. 2019 Oct 28:2019:6768571. doi: 10.1155/2019/6768571. eCollection 2019.

Authors

Wan-Cheng Yu¹, Hai-Ying Chen², Hong-Li Yang², Peng Xia³, Cheng-Wei Zou¹, Tong-Wen Sun⁴, Le-Xin Wang^{3

5}

Affiliations

¹ Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China.
² Central Laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
³ Department of Cardiology, Liaocheng People's Hospital and Affiliated Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong 252000, China.
⁴ Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou 450052, China.
⁵ School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

Abstract

Background/objectives: Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3η signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 (Cav-1^F92A) gene may enhance NO production. This study explored the effect of Cav-1^F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1^F92A) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3η signal transduction in a rat model of monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH).

Method: PAH was induced in rats through the subcutaneous injection of MCT. Next, rBMSC/Vector (negative control), rBMSC/Cav-1, rBMSC/Cav-1^F92A, or rBMSC/Cav-1^F92A+L-NAME were administered to the rats. Changes in pulmonary hemodynamic and vascular morphometry and oxidative stress levels were evaluated. CA1/kininogen and SelW/14-3-3η signal transduction, endothelial nitric oxide synthase (eNOS) dimerization, and eNOS/NO/sGC/cGMP pathway changes were determined through real-time polymerase chain reaction, Western blot, or immunohistochemical analyses.

Results: In MCT-induced PAH rats, rBMSC/Cav-1^F92A treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3η signal transduction; and reactivated the NO pathway.

Conclusions: In a rat model of MCT-induced PAH, rBMSC/Cav-1^F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.