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

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-...

Full description

Saved in:
Bibliographic Details
Main Authors: Wan-cheng Yu, Hai-ying Chen, Hong-li Yang, Peng Xia, Cheng-wei Zou, Tong-wen Sun, Le-xin Wang
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/6768571
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849395487733448704
author Wan-cheng Yu
Hai-ying Chen
Hong-li Yang
Peng Xia
Cheng-wei Zou
Tong-wen Sun
Le-xin Wang
author_facet Wan-cheng Yu
Hai-ying Chen
Hong-li Yang
Peng Xia
Cheng-wei Zou
Tong-wen Sun
Le-xin Wang
author_sort Wan-cheng Yu
collection DOAJ
description 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.
format Article
id doaj-art-a753ece67daf4f6187905b801d67b140
institution Kabale University
issn 1687-966X
1687-9678
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-a753ece67daf4f6187905b801d67b1402025-08-20T03:39:36ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/67685716768571rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal TransductionWan-cheng Yu0Hai-ying Chen1Hong-li Yang2Peng Xia3Cheng-wei Zou4Tong-wen Sun5Le-xin Wang6Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, ChinaCentral Laboratory of Liaocheng People’s Hospital, Liaocheng, Shandong 252000, ChinaCentral Laboratory of Liaocheng People’s Hospital, Liaocheng, Shandong 252000, ChinaDepartment of Cardiology, Liaocheng People’s Hospital and Affiliated Liaocheng People’s Hospital of Shandong University, Liaocheng, Shandong 252000, ChinaDepartment of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, ChinaDepartment of General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou 450052, ChinaDepartment of Cardiology, Liaocheng People’s Hospital and Affiliated Liaocheng People’s Hospital of Shandong University, Liaocheng, Shandong 252000, ChinaBackground/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.http://dx.doi.org/10.1155/2019/6768571
spellingShingle Wan-cheng Yu
Hai-ying Chen
Hong-li Yang
Peng Xia
Cheng-wei Zou
Tong-wen Sun
Le-xin Wang
rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
Stem Cells International
title rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
title_full rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
title_fullStr rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
title_full_unstemmed rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
title_short rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction
title_sort rbmsc cav 1f92a mediates oxidative stress in pah rat by regulating selw 14 3 3η and ca1 kininogen signal transduction
url http://dx.doi.org/10.1155/2019/6768571
work_keys_str_mv AT wanchengyu rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT haiyingchen rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT hongliyang rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT pengxia rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT chengweizou rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT tongwensun rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction
AT lexinwang rbmsccav1f92amediatesoxidativestressinpahratbyregulatingselw1433ēandca1kininogensignaltransduction