Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Chen, Li; Tao, Yong; Jiang, Yanrong

doi:10.1007/s11427-015-4861-0

Cited by 32 publications

(26 citation statements)

References 42 publications

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“…2A and B). These findings indicated that hypoxia was able to effectively activate the PI3K/AKT pathway, and that LY294002 was a potent inhibitor of the PI3K/AKT pathway, which is consistent with the results of previous studies (24,25). …”

Section: Resultssupporting

confidence: 92%

Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells

Sheng

Mao

et al. 2016

Experimental and Therapeutic Medicine

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Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been demonstrated to be an effective way of augmenting angiogenesis of ischemic tissue. The low oxygen conditions in ischemic tissue directly affect the biological behavior of engrafted cells. However, to date, the mechanism through which hypoxia regulates self-renewal, differentiation and paracrine function of BM-MSCs remains unclear. Clarification of this mechanism would be beneficial to the use of stem cell-based therapy. The PI3K/AKT pathway has been extensively investigated for its role in cell proliferation, cell transformation, paracrine function and angiogenesis. The present study aimed to analyze the role of PI3K/AKT pathway in hypoxia-induced proliferation of BM-MSCs and their differentiation into endothelial cells in vitro by the application of LY294002, a PI3K/AKT pathway inhibitor, with cells cultured in normoxia serving as a control. The results showed that rat BM-MSCs at passage 3 and 4 displayed only few phenotypical differences in the expression of surface antigens as detected by flow cytometry. When compared with the cells treated in normoxia, the proliferation of BM-MSCs in hypoxia was promoted, a greater number of cells expressed CD31 and a higher expression of vascular endothelial growth factor was observed after culture in hypoxic conditions. However, by inhibiting with LY294002, these changes induced by hypoxia were partly inhibited. In conclusion, the present study showed that the PI3K/AKT pathway served an important role in hypoxia-enhanced in vitro proliferation of BM-MSCs and their differentiation into endothelial cells and paracrine vascular endothelial growth factor.

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Section: Resultssupporting

confidence: 92%

Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells

Sheng

Mao

et al. 2016

Experimental and Therapeutic Medicine

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“…Along the same line, Chen et al . have recently described that apelin induces inflammatory signalling pathways in the BV2 microglial cell line33. In the present study, brain Il1beta and Inos mRNA levels were increased in apelin-treated mice, reinforcing the inflammatory role of apelin in the hypothalamus.…”

Section: Discussionsupporting

confidence: 82%

“…Given that, first, a positive correlation exists between apelin and inflammation during metabolic diseases32 and, second, an inflammatory induction was demonstrated in microglial cells culture in response to apelin33, we have decide to measure the variations of specific pro-inflammatory markers expressed in the entire hypothalamus. We found that chronic icv treatment significantly increases Interleukin-1 beta (Il1beta) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice

Drougard

Fournel

Marlin

et al. 2016

Sci Rep

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Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.

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“…ERK1/2 signaling has also been implicated in the proliferation and autophagy of lung adenocarcinoma cells when stimulated with apelin [43]. Additionally, apelin-mediated ERK signaling has also been shown to regulate cardiomyocyte hypertrophy and to activate the expression of inflammatory cytokines in microglial cells [44,45]. Our results show that ML221 treatment decreased Mz-ChA-1 tumor expression of p-ERK and t-ERK, indicating that this pathway may become less active with ML221 treatment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

et al. 2017

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Purpose Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. Methods Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz-ChA-1 cells were treated with increasing concentrations of apelin and ML221, an APLNR antagonist. Expression of proliferative and angiogenic genes were measured via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice, which were treated with ML221 (150 μg/kg) via tail vein injection. Results Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA proliferation and angiogenesis was inhibited by ML221 treatment. ML221 treatment significantly decreased tumor growth in nu/nu mice. Conclusion The apelin/APLNR axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has the potential to serve as a novel, tumor directed therapy for CCA.

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Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Cited by 32 publications

References 42 publications

Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells

Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

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