The stimulatory effects of eNOS/F92A-Cav1 on NO production and angiogenesis in BMSCs

Xia, Peng; Chen, Haiying; Chen, Shuangfeng; Wang, Lei; Strappe, Pádraig; Yang, Hongli; Zhou, Changhui; Zhang, Xiao; Zhang, Yingxin; Ma, Lei; Wang, Lexin

doi:10.1016/j.biopha.2015.11.001

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…Cav-1 F92A , which attenuates the inhibition of eNOS activity, enhances the production of NO. Moreover, it has been demonstrated the stimulatory effects of Cav-1 F92A on angiogenesis in rBMSCs via improving NO production, which may provide a novel treatment for PAH [17]. We hypothesized that in rats with MCT-induced PAH, the administration of rBMSC/Cav-1 F92A may ameliorate vascular resistance and restore pulmonary hemodynamics by inhibiting excessive oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…rBMSC isolation, culture, lentiviral vector (LV) packaging, and transduction were all performed as previously described [17]. Briefly, rBMSCs (passage 3) in the exponential growth phase were randomly divided into five groups: control group, rBMSC/Vector group (transduced with pLVX-mCMV-mCherry lentivirus), rBMSC/Cav-1 group (transduced with LV-Cav-1 lentivirus), rBMSC/Cav-1 F92A group (transduced with LV-Cav-1 F92A lentivirus), and rBMSC/Cav-1 F92A +L-NAME group (transduced with LV-Cav-1 F92A lentivirus and treated with L-NAME (2 mM, Beyotime Biotechnology, Jiangsu, China)).…”

Section: Methodsmentioning

confidence: 99%

“…Let-7a-modified MSCs ameliorate the progression of PAH and thus represent a promising therapeutic strategy for this disease [16]. We previously found that a mutated caveolin-1 (Cav-1 F92A ) gene that exhibits an alanine substitution for phenylalanine at position 92 modulates NO production in rat bone marrow mesenchymal stem cells (rBMSCs) [17]. Phenylalanine 92 (F92) is critical for the inhibitory actions of Cav-1 against endothelial nitric oxide synthase (eNOS), which inhibits NO production.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Yang

et al. 2019

Stem Cells International

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Chen

Yang

et al. 2019

Stem Cells International

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“…S0021; Beyotime Institute of Biotechnology, Haimen, China) according to the manufacturer's protocol. The assay was based on the Greiss test (26). Mice were euthanized, brains (n=5) were quickly removed, and tissues were homogenized in radioimmunoprecipitation assay lysis buffer (Beyotime Institute of Biotechnology) and centrifuged at 15,000 × g for 15 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

microRNA‑155 induces protection against cerebral ischemia/reperfusion injury through regulation of the Notch pathway in�vivo

Jiang

Zhou

et al. 2019

Exp Ther Med

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microRNA (miR)-155 has been demonstrated to participate in the regulation of endothelium during cerebral ischemia. In the present study, it was aimed to investigate the molecular mechanism of miR-155 in the regulation of cerebral ischemia/reperfusion (I/R) injury with middle cerebral artery occlusion (MCAO) in mice. The MCAO model was established in C57BL/6 mice. Transfection of miR-155 mimics and miR-155 inhibitors was performed to alter the expression of miR-155. The level of miR-155 was measured by RT-qPCR analysis. The western blotting results demonstrated that deletion of miR-155 increased the expression of Notch1, intracellular Notch receptor domain (NICD) and hairy and enhancer of split-1 (Hes1) levels. In addition, the percentage of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and caspase-3 levels were decreased following treatment with a miR-155 inhibitor compared with the Pre-IR group. Notably, disrupting miR-155 also increased nitric oxide (NO) production and the expression of endothelial NO synthase (eNOS), leading to downregulation of brain water content and Evans blue levels. However, overexpression of miR-155 restored all these changes to similar levels observed in the cerebral I/R injury group. The expressions of Notch1, NICD and Hes1 were also decreased to the cerebral I/R injury condition. In conclusion, a novel mechanism was identified for abrogating normal NO production and eNOS expression via the aberrant expression of the Notch signaling pathway, a mechanism that may be modulated by miR-155. Together, these results reveal important functions of miR-155 in regulating the Notch signaling pathway of the nervous system, and a potential role for miR-155 as a crucial therapy target for cerebral stroke.

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“…Lentiviral vector packaging and transduction was performed as we described previously with slight modification [ 32 ]. Briefly, lentiviral plasmids expressing ZNF750 gene, together with packaging plasmids pRSV-Rev, VSV-G and psPax2 were co-transfected into 70–80% confluent 293T cells with lipofectamine 2000 (Thermo Fisher Scientific, Waltham, MA, USA), according to the manufacturer’s instructions for the generation of LV-ZNF750 lentivirus.…”

Section: Methodsmentioning

confidence: 99%

Pathway-focused PCR array profiling of CAL-27 cell with over-expressed ZNF750

et al. 2017

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Zinc-finger protein 750 (ZNF750) is the potential anti-cancer gene in oral squamous cell carcinoma (OSCC). The present study was to investigate the expression changes of ZNF750 in OSCC tissue and to reveal the induction of altered mRNA expression profiles caused by over-expressed ZNF750 in CAL-27 cell. The expression level of ZNF750 in tissue specimens from OSCC patients was detected by immunohistochemistry. Gene expression profiling was performed using Human Signal Transduction PathwayFinder RT2 Profiler™ PCR Array. The expression changes of 84 key genes representing 10 signal transduction pathways in human following over-expressed ZNF750 in CAL-27 cell was examined. The expression of ZNF750 protein was reduced in OSCC tissues. The R2 PCR Array analysis revealed that 39 of the 84 examined genes that changed at least a two-fold between control and ZNF750 groups. These genes related to oxidative stress, WNT, JAK/STAT, TGFβ, NF-kappaB (NFκB), p53, Notch, Hedgehog, PPAR and Hypoxia signaling. ZNF750 could inhibit the candidate genes ATF4, SQSTM1, HMOX1, CCND1, TNF-alpha, TNFSF10 and FOSL1 but activate CDKN1A and EMP1. Our studies suggest that ZNF750 can regulate signaling pathways that related to proliferation, cell cycle, inflammation and oxidative stress in CAL-27 cell.

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The stimulatory effects of eNOS/F92A-Cav1 on NO production and angiogenesis in BMSCs

Cited by 12 publications

References 25 publications

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

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

microRNA‑155 induces protection against cerebral ischemia/reperfusion injury through regulation of the Notch pathway in�vivo

Pathway-focused PCR array profiling of CAL-27 cell with over-expressed ZNF750

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The stimulatory effects of eNOS/F92A-Cav1 on NO production and angiogenesis in BMSCs

Cited by 12 publications

References 25 publications

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

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

microRNA‑155 induces protection against cerebral ischemia/reperfusion injury through regulation of the Notch pathway in�vivo

Pathway-focused PCR array profiling of CAL-27 cell with over-expressed ZNF750

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Product

Resources

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

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