Rosuvastatin elicits KDR-dependent vasculogenic response of human placental stem cells through PI3K/AKT pathway

Cantoni, Silvia; Cavallini, Claudia; Bianchi, Francesca; Bonavita, Francesca; Vaccari, Valentina; Olivi, Elena; Frascari, Irene; Tassinari, Riccardo; Valente, Sabrina; Lionetti, Vincenzo; Ventura, Carlo

doi:10.1016/j.phrs.2011.12.004

Cited by 22 publications

(16 citation statements)

References 34 publications

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“…So far, the pro-angiogenic effect of statins has been ascribed to the activation of the Akt/GSK-3β/β-catenin pathway, which increases transcription of HIF-1α [24]. Vasculogenic response of human placental stem cells to rosuvastatin has also been attributed to the increase in VEGF expression through activation of the PI3K/Akt signaling [36]. However, the Akt-dependent angiogenic mechanism may also be mediated by inhibition of PHD.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat

Thirunavukkarasu¹,

Selvaraju²,

Dunna³

et al. 2013

International Journal of Cardiology

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Section: Discussionmentioning

confidence: 99%

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat

Thirunavukkarasu¹,

Selvaraju²,

Dunna³

et al. 2013

International Journal of Cardiology

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“…In the present study, we found that SV/SV‐NPs promoted PDGF‐BB secretion and that imatinib down‐regulated the increasing PDGF‐BB secretion induced by SV/SV‐NPs. Earlier studies also showed that statins enhanced the expression of PDGFR and PDGF, so we believe that SV/SV‐NPs may up‐regulate PDGF‐BB secretion in the recovery of barrier functions. A previous study reported that IQGAP1 bound directly to vascular endothelial growth factor receptor‐2 (VEGFR2) to transmit the VEGFR2 signal and promote endothelial cell migration .…”

Section: Discussionmentioning

confidence: 59%

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

Zheng

Zhang

Wang

2019

J Cellular Molecular Medi

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Endothelial barrier dysfunction is a critical pathophysiological process of sepsis. Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction. Statins may have a protective effect on endothelial barrier function. However, the effect and mechanism of statins on lipopolysaccharide (LPS)‐induced endothelial barrier dysfunction remain unclear. Simvastatin (SV) was loaded in nanostructured lipid carriers to produce SV nanoparticles (SV‐NPs). Normal SV and SV‐NPs were used to treat human umbilical vein vascular endothelial cells (HUVECs) injured by LPS. Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay. LY294002 and imatinib were used to inhibit the activity of PI3K/Akt and platelet‐derived growth factor receptor (PDGFR) β. IQ‐GTPase‐activating protein 1 (IQGAP1) siRNA was used to knockdown endogenous IQGAP1, which was used to verify the role of the PDGFRβ/PI3K/Akt/IQGAP1 pathway in SV/SV‐NPs‐mediated barrier protection in HUVECs injured by LPS. The results show that SV/SV‐NPs promoted the migration and decreased the permeability of HUVECs treated with LPS, and the efficacy of the SV‐NPs exceeded that of SV significantly. LY294002, imatinib and IQGAP1 siRNA all suppressed the barrier protection of SV/SV‐NPs. SV/SV‐NPs promoted the secretion of platelet‐derived growth factor‐BB (PDGF‐BB) and activated the PDGFRβ/PI3K/Akt/IQGAP1 pathway. SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRβ/PI3K/Akt/IQGAP1 pathway and PDGF‐BB secretion. As an appropriate formulation for restoring endothelial dysfunction, SV‐NPs may be more effective than SV.

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“…Transcribed silencing genes mediated by double-stranded RNA molecules can efficiently and specifically inhibit the expression of various genes associated with cancer incidence and drug resistance, and they are widely used in cancer and genetic research, opening up a new path for the effective treatment of tumors (Curtin et al, 2012). KDR is widely distributed in vascular endothelial cells and plays an important role in their growth and differentiation; it can increase vascular permeability and promote angiogenesis and vascular endothelial cell proliferation, and has become a focus for research in recent years (Adham and Coomber, 2009;Cantoni et al, 2012).Typically, the renewal of vascular endothelial cells is slow, while the proliferation of endothelial cells in tumor tissues is active, and KDR is highly expressed to mediate the generation of vascular endothelial growth factor in tumor angiogenesis (Kim et al, 2006;Holmes and Zachary, 2008). Chemotherapy is critical in the comprehensive treatment of lung cancer, and erlotinib is one of the most common and the most effective chemotherapy drugs for lung cancer (Vickers et al, 2012;Renouf et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the incidence, invasion, and migration of lung cancer are involved in the activation and deactivation of various genes (Iannolo et al, 2011). A study by Cantoni et al (2012) found that the kinase insert domain receptor (KDR) gene plays an important role in lung adenocarcinoma cell proliferation, which can be used as a new target for cancer therapy. Chemotherapy is critical in the comprehensive treatment of lung cancer, and erlotinib is one of the most common and the most effective chemotherapy drugs for lung cancer (Renouf et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of kinase insert domain receptor (KDR) gene silencing on the sensitivity of A549 cells to erlotinib

Zhu¹,

Liu²

2015

Genet. Mol. Res.

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ABSTRACT. We investigated the effects of kinase insert domain receptor (KDR) gene silencing on the proliferation of A549 cells and their sensitivity to erlotinib. A KDR small interfering RNA (siRNA) sequence was designed and synthesized; then, it was transfected into A549 cells using Lipofectamine TM 2000. KDR mRNA and protein expression after KDR gene silencing was detected by reverse transcription polymerase chain reaction and western blotting; the A549 cell cycle was detected by flow cytometry. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay were performed to determine the sensitivity of A549 cells to erlotinib after KDR gene silencing. After 48h of KDR gene silencing, there was a significant decrease in KDR gene and protein expression (P < 0.05). The A549 cell cycle was arrested at the G0/G1 phase, and the number of cells in the S phase decreased; the difference was statistically significant (P < 0.05). In the KDR gene silencing group, the sensitivity of A549 cells to erlotinib was significantly enhanced (P < 0.05). KDR siRNA can significantly silence the KDR gene in A549 cells, inhibit the proliferation of A549 cells, and enhance their sensitivity to erlotinib.

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Rosuvastatin elicits KDR-dependent vasculogenic response of human placental stem cells through PI3K/AKT pathway

Cited by 22 publications

References 34 publications

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

Effects of kinase insert domain receptor (KDR) gene silencing on the sensitivity of A549 cells to erlotinib

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