Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells

Wang, Yingyi; Yan, Wei; Lu, Xiaoming; Qian, Chunfa; Zhang, Junxia; Li, Ping; Shi, Lei; Zhao, Peng; Fu, Zhen-Yan; Pu, Peiyu; Kang, Chunsheng; Jiang, Tao; Liu, Ning; You, Yongping

doi:10.1016/j.ejcb.2011.03.005

Cited by 88 publications

(76 citation statements)

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“…P85β, i.e., PIK3R2, inhibits phosphorylation of Akt, which is subsequently activated by PI3K. The PI3K/Akt signaling pathway mediates many biological activities in EPCs including proliferation [8], endothelial differentiation [9], migration [10], senescence [11], and hormonal secretion [12]. However, the role of PI3K/Akt signaling in EndMT of EPCs is unclear.…”

Section: Introductionmentioning

confidence: 99%

Activated Phosphatidylinositol 3-Kinase/Akt Inhibits the Transition of Endothelial Progenitor Cells to Mesenchymal Cells by Regulating the Forkhead Box Subgroup O-3a Signaling

Zhang¹,

Zhang²,

Zhou³

et al. 2015

Cell Physiol Biochem

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Background and Aims: Endothelial progenitor cells (EPCs) differentiate into mature endothelial cells and may thus be candidates for ischemic disease therapy; however, the transition of EPCs to mesenchymal cells is not fully understood. We explored the role of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGF-β1). Methods: Rat bone marrow-derived EPCs were isolated by using Ficoll-Isopaque Plus density-gradient centrifugation. EndMT was induced by TGF-β1 (5 ng/mL). PI3K/Akt signaling was activated by IGF-1 or Lenti-PIK3R2 shRNA. Additionally, FoxO3a expression was suppressed by a lentiviral vector (Lenti-FoxO3a shRNA). Smad3 and FoxO3a co-localization was detected by confocal immunofluorescence microscopy. The expressions of molecules involved in EndMT were exmined by using Western-blot analysis. Results: EndMT of EPCs was fully developed after TGF-β1 treatment (5 ng/mL) for 7 days. PIK3R2 expression in EPCs was driven by TGF-β1. Lenti-PIK3R2 shRNA blocked alpha-smooth muscle actin (α-SMA) expression in EPCs treated with TGF-β1, drove PI3K/Akt activation, and increased expression of phosphorylated FoxO3a instead of phosphorylated Smad3. The effect of Lenti-PIK3R2 shRNA was reduced by LY294002, a specific inhibitor of PI3K. IGF-1 attenuated α-SMA protein expression in EPCs treated with TGF-β1. Similar to Lenti-PIK3R2 shRNA, IGF-1 also inhibited and elevated the phosphorylation of Smad3 and FoxO3a, respectively. IGF-1 disrupted the co-localization of these proteins in EPCs treated with TGF-β1. Lenti-FoxO3a shRNA transfection of EPCs suppressed expression of FoxO3a as well as that of the mesenchymal markers SM22α and α-SMA. Conclusions: Activation of PI3K/Akt signaling by Lenti-PIK3R2 shRNA or by exogenous IGF-1 inhibits EndMT in EPCs via negative regulation of FoxO3a-dependent signaling.

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Section: Introductionmentioning

confidence: 99%

Activated Phosphatidylinositol 3-Kinase/Akt Inhibits the Transition of Endothelial Progenitor Cells to Mesenchymal Cells by Regulating the Forkhead Box Subgroup O-3a Signaling

Zhang¹,

Zhang²,

Zhou³

et al. 2015

Cell Physiol Biochem

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“…Previously, an increased VEGF production and activated PI3K signaling pathway have been observed in OPN-stimulated endothelial cells, suggesting that VEGF may be the candidate target for the modulation of NPC [19,20]. In this study, we examined the regulatory effect of rhOPN on EZH2 expression in vitro in order to clarify the possible role of EZH2 in OPN-stimulated NPC progression.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Promotes EZH2 Expression and Tumor Progression in Nasopharyngeal Carcinoma

Luo

Feng

et al. 2014

ORL

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Objective: To evaluate the possible mechanism of osteopontin (OPN) in the tumor progression of nasopharyngeal carcinoma (NPC). Methods: Twenty NPC specimens and 10 normal biopsy specimens were analyzed, and the expression of OPN and enhancer of zeste homolog 2 (EZH2) was examined by immunohistochemical staining. Moreover, the expression of EZH2 in NPC cell lines was examined using quantitative reverse transcription polymerase chain reaction and Western blot analysis in the presence of recombinant human (rh) OPN and specific inhibitors. NPC cell migration and invasion were evaluated using a transwell chamber in the presence of rhOPN and/or EZH2 siRNA. Results: The immunoreactivity of OPN and EZH2 was significantly enhanced in NPC specimens compared with the normal controls (p < 0.05). EZH2 expression in NPC specimens was significantly associated with OPN expression and tumor stage (p < 0.05). Moreover, rhOPN significantly stimulated EZH2 expression in the NPC cell line through a MAPK-mediated pathway and significantly stimulated migration and invasion of the NPC cell line (p < 0.05), which was notably inhibited by EZH2 siRNA transfection (p < 0.05). Conclusion: Our findings suggest that OPN may promote tumor progression of NPC through an EZH2-dependent pathway. i 2014 S. Karger AG, Basel

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“…L'OPN interagit via son domaine RGD avec les intégrines v3 présentes à la surface des cellules endothéliales et induit la voie de signalisation PI3K (phosphoinositide 3-kinase)/Akt (protéine kinase B) menant à l'activation de l'eNOS (endothelial NO synthase) et à la production de NO (monoxyde d'azote). Celui-ci induit la prolifération et la migration des cellules endothéliales ainsi que la formation de tubes [43]. L'influence de l'OPN sur la genèse de nouveaux capillaires infiltrant les tumeurs a été démontrée dans de nombreux modèles in vitro et in vivo [44,45].…”

Section: Angiogenèseunclassified

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et al. 2013

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Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells

Cited by 88 publications

References 20 publications

Activated Phosphatidylinositol 3-Kinase/Akt Inhibits the Transition of Endothelial Progenitor Cells to Mesenchymal Cells by Regulating the Forkhead Box Subgroup O-3a Signaling

Activated Phosphatidylinositol 3-Kinase/Akt Inhibits the Transition of Endothelial Progenitor Cells to Mesenchymal Cells by Regulating the Forkhead Box Subgroup O-3a Signaling

Osteopontin Promotes EZH2 Expression and Tumor Progression in Nasopharyngeal Carcinoma

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