Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3[eta] and CA1/Kininogen Signal Transduction

Background/Objectives. Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3[eta] signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 ([Cav-1.sup.F92A]) gene may enhance NO production. This study explored the eff...

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Published inStem cells international
Main Authors Yu, Wan-cheng, Chen, Hai-ying, Yang, Hong-li, Xia, Peng, Zou, Cheng-wei, Sun, Tong-wen, Wang, Le-xin
Format Journal Article
LanguageEnglish
Published Hindawi Limited 30.11.2019
Subjects
Cellular signal transduction
Nitric oxide
Oxidative stress
Pulmonary hypertension
Sapropterin dihydrochloride
Stem cells
China
California
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Summary:Background/Objectives. Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3[eta] signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 ([Cav-1.sup.F92A]) gene may enhance NO production. This study explored the effect of [Cav-1.sup.F92A]- modified rat bone marrow mesenchymal stem cells ([rBMSC/Cav-1.sup.F92A]) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3[eta] 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.sup.F92A], or [rBMSC/Cav-1.sup.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/14-3-3[eta] 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.sup.F92A] treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3[eta] signal transduction; and reactivated the NO pathway. Conclusions. In a rat model of MCT-induced PAH, [rBMSC/Cav-1.sup.F92A] reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3[eta] signal transduction.
ISSN:1687-9678
1687-9678
DOI:10.1155/2019/6768571