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

• Published in: Stem cells international Vol. 2019; no. 2019; pp. 1 - 11
• Main Authors: Wang, Le-xin, Zou, Cheng-wei, Xia, Peng, Yang, Hong-li, Chen, Hai-ying, Yu, Wan-cheng, Sun, Tong-wen
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019; Hindawi; Hindawi Limited; Wiley
• Subjects: Blood pressure; Bone marrow; Carbonic anhydrase; Carbonic anhydrases; Caveolin; Caveolin-1; Cyclic GMP; Dimerization; Gene expression; Heart; Hemodynamics; Hypertension; Kinases; Kininogens; Laboratory animals; Lungs; Mesenchyme; Monocrotaline; Morphometry; NG-Nitroarginine methyl ester; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Physiology; Polymerase chain reaction; Proteins; Pulmonary arteries; Pulmonary hypertension; Rodents; Selenoprotein W; Signal transduction; Stem cell transplantation; Stem cells; Stenosis; Systolic pressure; Veins & arteries; Ventricle; Beijing China; China
• ISSN: 1687-966X; 1687-9678
• DOI: 10.1155/2019/6768571

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-1F92A) gene may enhance NO production. This study explored the effect of Cav-1F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1F92A) 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-1F92A, or rBMSC/Cav-1F92A+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-1F92A 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-1F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.