ProBDNF is a novel mediator of the interaction between MDA-MB-231 breast cancer cells and brain microvascular endothelial cells

Brain Endothelial Cells ◽

Antiangiogenic Effect ◽

Aim: The aim of the current work is to assess the role of proBDNF/BDNF in the interaction between brain microvascular endothelial cells and MDA-MB-231 breast cancer cell line that has been consistently reported to cause brain metastasis. Background: Breast cancer brain metastasis (BM) is a significant health problem with limited therapeutic options. The development of BM is a multistep process that requires constant interaction with brain vasculature and development of tumor blood supply. The benefits of antiangiogenic modalities based on antagonizing vascular endothelial growth factor in breast cancer metastasis did not prove to be effective. Brain derived neurotrophic factor (BDNF) is a neurotrophin with reported angiogenic effect. There is a lack of data regarding the involvement of BDNF in metastatic breast cancer interaction with brain microvascular endothelial cells (HBEC-5i). Objectives: To determine the role of the pro form of BDNF in the interaction between MDA-MB-231 cells and brain endothelial cells. Methods: using an adaptive transfer design, the cross talk between HBEC-5i and MDA-MB-231 was investigated. HBEC-5i were treated with MDA-MB-231-conditioned media and the involvement of BDNF/proBDNF in the interaction was assessed using both release and inhibitor-based assays in migration and in vitro tube formation assay. Results: MDA-MB-231 and HBEC-5i released total BDNF (250 vs. 80 pg/ml, respectively). MDA-MB-231 conditioned media inhibited the migration of HBEC-5i by more than 80% (p<0.05) and tube formation by 75% (p<0.05). Neutralizing mature BDNF did not alter the MDA-MB-231 induced antiangiogenic effect which was completely blunted by antagonizing proBDNF. MDA-MB-231 released proBDNF (131.5 pg/ml) and more that 60% of total BDNF released was in the pro-form. Conclusion: proBDNF is a novel mediator of the breast cancer induced antiangiogenic effect in brain endothelial cells.

Hydroxysafflor yellow A promotes angiogenesis in rat brain microvascular endothelial cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R) through SIRT1-HIF-1α-VEGFA signaling pathway

Current Neurovascular Research ◽

10.2174/1567202618666211109104419 ◽

2021 ◽

Vol 18 ◽

Author(s):

Juxuan Ruan ◽

Lei Wang ◽

Jiheng Dai ◽

Jing Li ◽

Ning Wang ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Signaling Pathway ◽

Ischemia Reperfusion ◽

Tube Formation ◽

Hydroxysafflor Yellow A ◽

Objective: Angiogenesis led by brain microvascular endothelial cells (BMECs) contributes to the remission of brain injury after brain ischemia reperfusion. In this study, we investigated the effects of hydroxysafflor yellow A(HSYA) on angiogenesis of BMECs injured by OGD/R via SIRT1-HIF-1α-VEGFA signaling pathway. Methods: The OGD/R model of BMECs was established in vitro by OGD for 2h and reoxygenation for 24h. At first, the concentrations of vascular endothelial growth factor (VEGF), Angiopoietin (ang) and platelet-derived growth factor (PDGF) in supernatant were detected by ELISA, and the proteins expression of VEGFA, Ang-2 and PDGFB in BMECs were tested by western blot; the proliferation, adhesion, migration (scratch healing and transwell) and tube formation experiment of BMECs; the expression of CD31 and CD34 were tested by immunofluorescence staining. The levels of sirtuin1(SIRT1), hypoxia-inducible factor-1α (HIF-1α), VEGFA mRNA and protein were tested. Results: HSYA up-regulated the levels of VEGF, Ang and PDGF in the supernatant of BMECs under OGD/R, and the protein expression of VEGFA, Ang-2 and PDGFB were increased; HSYA could significantly alleviate the decrease of cell proliferation, adhesion, migration and tube formation ability of BMECs during OGD/R; HSYA enhanced the fluorescence intensity of CD31 and CD34 of BMECs during OGD/R; HSYA remarkably up-regulated the expression of SIRT1, HIF-1α, VEGFA mRNA and protein after OGD/R, and these increase decreased after SIRT1 was inhibited. Conclusion: SIRT1-HIF-1α-VEGFA signaling pathway is involved in HSYA improves angiogenesis of BMECs injured by OGD/R.

Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia/Reperfusion Injury

Neural Plasticity ◽

10.1155/2020/8814239 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Xutong Li ◽

Ye Zhang ◽

Yong Wang ◽

Dan Zhao ◽

Chengcheng Sun ◽

...

Keyword(s):

Endothelial Cells ◽

Reperfusion Injury ◽

Vascular Function ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tube Formation ◽

Significant Difference ◽

Background. Ischemic stroke is a severe acute cerebrovascular disease which can be improved with neuroprotective therapies at an early stage. However, due to the lack of effective neuroprotective drugs, most stroke patients have varying degrees of long-term disability. In the present study, we investigated the role of exosomes derived from CXCR4-overexpressing BMSCs in restoring vascular function and neural repair after ischemic cerebral infarction. Methods. BMSCs were transfected with lentivirus encoded by CXCR4 (BMSCCXCR4). Exosomes derived from BMSCCXCR4 (ExoCXCR4) were isolated and characterized by transmission electron microscopy and dynamic light scattering. Western blot and qPCR were used to analyze the expression of CXCR4 in BMSCs and exosomes. The acute middle cerebral artery occlusion (MCAO) model was prepared, ExoCXCR4 were injected into the rats, and behavioral changes were analyzed. The role of ExoCXCR4 in promoting the proliferation and tube formation for angiogenesis and protecting brain endothelial cells was determined in vitro. Results. Compared with the control groups, the ExoCXCR4 group showed a significantly lower mNSS score at 7 d, 14 d, and 21 d after ischemia/reperfusion ( P < 0.05 ). The bEnd.3 cells in the ExoCXCR4 group have stronger proliferation ability than other groups ( P < 0.05 ), while the CXCR4 inhibitor can reduce this effect. Exosomes control (ExoCon) can significantly promote the migration of bEnd.3 cells ( P < 0.05 ), while there was no significant difference between the ExoCXCR4 and ExoCon groups ( P > 0.05 ). ExoCXCR4 can further promote the proliferation and tube formation for the angiogenesis of the endothelium compared with ExoCon group ( P < 0.05 ). In addition, cobalt chloride (COCl2) can increase the expression of β-catenin and Wnt-3, while ExoCon can reduce the expression of these proteins ( P < 0.05 ). ExoCXCR4 can further attenuate the activation of Wnt-3a/β-catenin pathway ( P < 0.05 ). Conclusions. In ischemia/reperfusion injury, ExoCXCR4 promoted the proliferation and tube formation of microvascular endothelial cells and play an antiapoptotic role via the Wnt-3a/β-catenin pathway.

A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells

Scientific Reports ◽

10.1038/s41598-018-37495-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Binah baht Ysrayl ◽

Muthukumar Balasubramaniam ◽

Ife Albert ◽

Fernando Villalta ◽

Jui Pandhare ◽

...

Keyword(s):

Endothelial Cells ◽

Role of OmpA and IbeB in Escherichia coli K1 Invasion of Brain Microvascular Endothelial Cells In Vitro and In Vivo

Pediatric Research ◽

10.1203/00006450-200205000-00003 ◽

2002 ◽

Vol 51 (5) ◽

pp. 559-563 ◽

Cited By ~ 60

Author(s):

Ying Wang ◽

Kwang Sik Kim

Keyword(s):

Escherichia Coli ◽

Endothelial Cells ◽

Microvascular Endothelial ◽

Escherichia Coli K1

MicroRNA-126-3p Inhibits Angiogenic Function of Human Lung Microvascular Endothelial Cells via LAT1 (L-Type Amino Acid Transporter 1)-Mediated mTOR (Mammalian Target of Rapamycin) Signaling

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.313800 ◽

2020 ◽

Vol 40 (5) ◽

pp. 1195-1206 ◽

Cited By ~ 2

Author(s):

Danting Cao ◽

Andrew M. Mikosz ◽

Alexandra J. Ringsby ◽

Kelsey C. Anderson ◽

Erica L. Beatman ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Amino Acid ◽

Cell Apoptosis ◽

Human Lung ◽

Mammalian Target Of Rapamycin ◽

Tube Formation ◽

Objective: MicroRNA-126-3p (miR-126) is required for angiogenesis during organismal development or the repair of injured arterial vasculature. The role of miR-126 in lung microvascular endothelial cells, which are essential for gas exchange and for lung injury repair and regeneration, remains poorly understood. Considering the significant heterogeneity of endothelial cells from different vascular beds, we aimed to determine the role of miR-126 in regulating lung microvascular endothelial cell function and to elucidate its downstream signaling pathways. Approach and Results: Overexpression and knockdown of miR-126 in primary human lung microvascular endothelial cells (HLMVEC) were achieved via transfections of miR-126 mimics and antisense inhibitors. Increasing miR-126 levels in HLMVEC reduced cell proliferation, weakened tube formation, and increased cell apoptosis, whereas decreased miR-126 levels stimulated cell proliferation and tube formation. Whole-genome RNA sequencing revealed that miR-126 was associated with an antiangiogenic and proapoptotic transcriptomic profile. Using validation assays and knockdown approaches, we identified that the effect of miR-126 on HLMVEC angiogenesis was mediated by the LAT1 (L-type amino acid transporter 1), via regulation of mTOR (mammalian target of rapamycin) signaling. Furthermore, downregulation of miR-126 in HLMVEC inhibited cell apoptosis and improved endothelial tube formation during exposure to environmental insults such as cigarette smoke. Conclusions: miR-126 inhibits HLMVEC angiogenic function by targeting the LAT1-mTOR signaling axis, suggesting that miR-126 inhibition may be useful for conditions associated with microvascular loss, whereas miR-126 augmentation may help control unwanted microvascular angiogenesis.