Gene expression profiling of common signal transduction pathways affected by rBMSCs/F92A-Cav1 in the lungs of rat with pulmonary arterial hypertension

被引：5

作者：

Chen, Haiying ^{[1
,2
,3
,4
]}

Yang, Hongli ^{[1
,2
]}

Xu, Chong ^{[1
,2
]}

Yue, Hongmei ^{[3
,4
,5
,6
]}

Xia, Peng ^{[5
,6
]}

Strappe, Padraig Michael ^{[7
]}

Wang, Lei ^{[5
,6
]}

Pan, Li ^{[1
,2
]}

Tang, Wenqiang ^{[1
,2
]}

Chen, Shuangfeng ^{[1
,2
]}

Wang, Lexin ^{[5
,6
,7
]}

机构：

[1] Liaocheng Peoples Hosp, Cent Lab, Liaocheng 252000, Shandong, Peoples R China

[2] Liaocheng Peoples Hosp, Key Lab Oral & Maxillofacial Head & Neck Med Biol, Liaocheng 252000, Shandong, Peoples R China

[3] Taishan Med Univ, Liaocheng Peoples Hosp, Liaocheng, Shandong, Peoples R China

[4] Taishan Med Univ, Sch Clin, Liaocheng, Shandong, Peoples R China

[5] Shandong Univ, Liaocheng Peoples Hosp, Dept Cardiol, Liaocheng 252000, Shandong, Peoples R China

[6] Shandong Univ, Affiliated Liaocheng Peoples Hosp, Liaocheng 252000, Shandong, Peoples R China

[7] Charles Sturt Univ, Sch Biomed Sci, Wagga Wagga, NSW 2650, Australia

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2016年 / 83卷

基金：

中国国家自然科学基金;

关键词：

Bone marrow derived mesenchymal stem cells; Endothelial nitric oxide synthase; Caveolin-1; Nitric oxide; Pulmonary arterial hypertension; STRESS; CELL;

D O I：

10.1016/j.biopha.2016.06.028

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Pulmonary arterial hypertension (PAH) is associated with sustained vasoconstriction, inflammation and suppressed apoptosis of smooth muscle cells. Our previous studies have found that rat bone marrow-derived mesenchymal stem cells (rBMSCs) transduced with a mutant caveolin-1(F92A-Cav1) could enhance endothelial nitric oxide synthase (eNOS) activity and improve pulmonary vascular remodeling, but the potential mechanism is not yet fully explored. The present study was to investigate the gene expression profile upon rBMSCs/F92A-Cav1delivered to PAH rat to evaluate the role of F92A-Cav1 in its regulation. Methods: PAH was induced with monocrotaline (MCT, 60 mg/kg) prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1 or F92A-Cav1. Gene expression profiling was performed using Rat Signal Transduction PathwayFinder array. The expression changes of 84 key genes representing 10 signal transduction pathways in rat following rBMSCs/F92A-Cav1 treatment was examined. Results: Screening with the Rat Signal Transduction PathwayFinder R-2 PCR Array system and subsequent western blot, immunohistochemistry or real time PCR analysis revealed that F92A-Cav1 modified rBMSCs can inhibit the inflammation factors (TNF-alpha, Icam1 and C/EBPdelta), pro-proliferation genes (c-Myc, Bcl2a1d, Notch1and Hey2), oxidative stress gene (Hmox1) and activate cell cycle arrested gene Cdkn1a, ameliorating inflammation and inhibiting cell proliferation in PAH rat. Conclusion: rBMSCs/F92A-Cav1 inhibits inflammation and cell proliferation by regulating signaling pathways that related to inflammation, proliferation, cell cycle and oxidative stress. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：100 / 106

页数：7

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