scholarly journals DPP4 inhibitors promote biological functions of human endothelial progenitor cells by targeting the SDF-1/CXCR4 signaling pathway

2016 ◽  
Vol 68 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Feng Liu ◽  
Guo-Dong Huang ◽  
Jia-Zhen Tang ◽  
Yu-Huan Peng
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Hypoglycemic Agents ◽  
Dependent Manner ◽  
Biological Functions ◽  
Endothelial Progenitor ◽  
Cxcr4 Signaling ◽  
Dpp4 Inhibitors

Dipeptidyl peptidase 4 (DPP4) inhibitors(oral hypoglycemic agents)have beneficial effects during the early stages of diabetes. In this study, we evaluated the role of DPP4inhibitorsonthe biological functions of cultured human endothelial progenitor cells (EPCs). After treating EPCs with the DPP4 inhibitors sitagliptin and vildagliptin, we examined the mRNA expression of DPP4, vascular endothelial growth factor (VEGF),VEGF receptor 2 (VEGFR-2),endothelial nitric oxide synthase (eNOS), caspase-3,stromal cell-derived factor-1 (SDF-1), chemokine (C-X-C motif) receptor 4 (CXCR4) were measured by RT-PCR. The protein expression of SDF-1 and CXCR4 was determined by Western blot; cell proliferation was tested by the MTT method, and DPP4 activity was determined by a DPP4 assay. Our results revealed that DPP4 expression and activity were inhibited following the treatment with various doses of DPP4 inhibitors. Cell proliferation and the expression of VEGF, VEGFR-2andeNOS were up regulated, while cell apoptosis was inhibited by DPP4 inhibitors in a dose-dependent manner. DPP4 inhibitors activated the SDF-1/CXCR4 signaling pathway, shown by the elevated expression of SDF-1/CXCR4. This further proved that after the SDF-1/CXCR4 signaling pathway was blocked by its inhibitor ADM3100, the effects of DPP4 inhibitors on the proliferation and apoptosis, and the expression of VEGF, VEGFR-2and eNOS of EPCs were significantly reduced. These findings suggest that DPP4 inhibitors promote the biological functions of human EPCs by up regulating the SDF-1/CXCR4 signaling pathway.

scholarly journals Adiponectin Enhances Biological Functions of Vascular Endothelial Progenitor Cells Through the mTOR-STAT3 Signaling Pathway

2018 ◽  
pp. 563-570 ◽  
Author(s):  
X. DONG ◽  
X. YAN ◽  
W. ZHANG ◽  
S. TANG
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Vascular Endothelial ◽  
Biological Functions ◽  
Endothelial Progenitor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro. After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western blot. It was suggested that APN promoted the optical density (OD) value of VEPCs, enhanced mRNA expression of Bcl-2 and VEGF, and inhibited cell apoptotic rate. Furthermore, protein expression of pSTAT3 was also increased in the presence of APN. Moreover, APN changed-proliferation, apoptosis and VEGF expression of VEPCs were partially suppressed after blocking the mTOR-STAT3 signaling pathway by the mTOR inhibitor XL388. It was indicated that APN promoted biological functions of VEPCs through targeting the mTOR-STAT3 signaling pathway.

Abstract TP275: “Touch-and-Go”: Touching of Endothelial Cells by Endothelial Progenitor Cells Increases Activation of Pro-survival ERK1/2 Signaling

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Emiri T Mandeville ◽  
Su Jing Chen ◽  
Kazuhide Hayakawa ◽  
Ken Arai ◽  
Eng H Lo
Keyword(s):  
Endothelial Cells ◽  
Rat Brain ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Short Duration ◽  
Intracellular Signaling ◽  
Infarct Volume ◽  
Dependent Manner ◽  
Brain Endothelial Cells ◽  
Endothelial Progenitor

Background: Cell-based therapies can potentially promote neurological repair for CNS diseases including stroke. Pre-clinical data showed improved infarct volume and neurological scores following injection of Endothelial progenitor cells (EPCs). However relatively few EPCs were found in infarct areas, and mechanisms by which injected EPCs enhance neovascularization are largely unknown. In this study, we hypothesized that circulating EPCs would positively impact intracellular signaling cascades in rat brain endothelial cells (RBECs) even by short-duration contact due to activation of pro-survival ERK1/2 cascades. Methods: Primary RBECs and EPCs were isolated from rat brain and spleen, respectively. These cells were cultured separately, and 10 days later, cultured EPCs were transferred to plates of cultured RBECs. After 1 or 10 min incubation with cell-culture plate shaking, EPCs were washed from the plates and RBECs were subjected to western blot analysis to assess ERK1/2 phosphorylation. As a negative control for EPCs, we prepared neutrophils from different rats. Results: We confirmed that our RBECs and EPCs were viable in vitro by LDH assay and these cells were positive for their cell-type markers assessed by immunostaining. Ten min incubation of EPCs phosphorylated ERK1/2 in RBECs in an EPC-number-dependent manner, whereas identical conditions of neurtrophil incubation did not. Importantly, only 1 min incubation with EPCs significantly upregulated ERK cascades in RBECs. Remaining EPCs on RBEC surfaces may not contribute to ERK1/2 phosphorylation because very few EPCs were observed after washout. In addition, experiments by the same procedure without RBECs did not show ERK phosphorylation. Conclusion: We demonstrated increased activation of pro-survival ERK1/2 signaling in RBECs following short-duration incubation of EPCs. Results suggest that circulating EPCs may not need to be integrated into existing blood vessels to promote neovascularization. Rather, short-duration interactions between EPCs and RBECs may provide a “Touch-and-Go” stimulus that supports brain endothelial cells to make favorable environments for neovascularization.

scholarly journals Protective Effect of Silymarin against Rapamycin-induced Apoptosis and Proliferation Inhibition in Endothelial Progenitor Cells

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Concentration Dependent Manner ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).

Endothelial progenitor cells proliferated via MEK-dependent p42 MAPK signaling pathway

2014 ◽  
Vol 400 (1-2) ◽  
pp. 201-206 ◽  
Author(s):  
Ferry Sandra ◽  
Yudi Her Oktaviono ◽  
Mohammad Aris Widodo ◽  
Yanni Dirgantara ◽  
Angliana Chouw ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Endothelial Progenitor
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