Heparin binding VEGF isoforms attenuate hyperoxic embryonic lung growth retardation via a FLK1-neuropilin-1-PKC dependent pathway

Esquibies, A.E.; Karihaloo, Anil; Quaggin, Susan E.; Bazzy‐Asaad, Alia; Cantley, Lloyd G.

doi:10.1186/1465-9921-15-32

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…S1B) for 72 or 24 hours, respectively, and cell viability measured. Concentration of anti-VEGF-A and -B antibodies, and VEGFR1, VEGFR2, and NRP1 was chosen according to the company's recommendation and in line with others, [32][33][34][35][36] in the same way as the selected the doses of recombinant VEGF-A and -B. 33,34,37,38 Anti-VEGF-B and VEGFR1 antibodies, 500 ng/mL and 10 μg/mL, respectively; NRP1 antibody, 30 μg/mL; 4-HNE 10 μM.…”

Section: Vegf-b Neutralization Compromises Müller Cell Viability and mentioning

confidence: 99%

VEGF-B Is an Autocrine Gliotrophic Factor for Müller Cells under Pathologic Conditions

Llorián-Salvador

Barabás

Byrne

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Müller glia are important in retinal health and disease and are a major source of retinal VEGF-A. Of the different VEGF family members, the role of VEGF-A in retinal health and disease has been studied extensively. The potential contribution of other VEGF family members to retinal pathophysiology, however, remains poorly defined. This study aimed to understand the role of VEGF-B in Müller cell pathophysiology. METHODS. The expression of different VEGFs and their receptors in human MIO-M1 and mouse QMMuC-1 Müller cell lines and primary murine Müller cells was examined by RT-PCR, ELISA, and Western blot. The effect of recombinant VEGF-B or VEGF-B neutralization on Müller cell viability and survival under normal, hypoxic, and oxidative (4-hydroxynonenal [4-HNE]) conditions was evaluated by Alamar Blue, Yo-Pro uptake, and immunocytochemistry. The expression of glial fibrillary acidic protein, aquaporin-4, inward rectifying K + channel subtype 4.1, glutamine synthetase, and transient receptor potential vanilloid 4 under different treatment conditions was examined by RT-PCR, immunocytochemistry, and Western blot. Transient receptor potential vanilloid 4 channel activity was assessed using a Fura-2-based calcium assay. RESULTS. VEGF-B was expressed in Müller cells at the highest levels compared with other members of the VEGF family. VEGF-B neutralization did not affect Müller cell viability or functionality under normal conditions, but enhanced hypoxia-or 4-HNE-induced Müller cell death and decreased inward rectifying K + channel subtype 4.1 and aquaporin-4 expression. Recombinant VEGF-B restored Müller cell glutamine synthetase expression under hypoxic conditions and protected Müller cells from 4-HNE-induced damage by normalizing transient receptor potential vanilloid 4 channel expression and activity. CONCLUSIONS. Autocrine production of VEGF-B protects Müller cells under pathologic conditions.

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Section: Vegf-b Neutralization Compromises Müller Cell Viability and mentioning

confidence: 99%

VEGF-B Is an Autocrine Gliotrophic Factor for Müller Cells under Pathologic Conditions

Llorián-Salvador

Barabás

Byrne

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…4 A ). As a receptor of vascular endothelial growth factor (VEGF) which regulates the vascular development and tumorigenesis, NRP-1 was usually considered to be overexpressed on both endothelial cells and tumor cells 11 , 34 , 35 . Herein, NRP-1 was found expressed on all the three cell lines.…”

Section: Resultsmentioning

confidence: 99%

Dual Receptor Recognizing Cell Penetrating Peptide for Selective Targeting, Efficient Intratumoral Diffusion and Synthesized Anti-Glioma Therapy

Liu¹,

Mei²,

Xu³

et al. 2016

Theranostics

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Cell penetrating peptides (CPPs) were widely used for drug delivery to tumor. However, the nonselective in vivo penetration greatly limited the application of CPPs-mediated drug delivery systems. And the treatment of malignant tumors is usually followed by poor prognosis and relapse due to the existence of extravascular core regions of tumor. Thus it is important to endue selective targeting and stronger intratumoral diffusion abilities to CPPs. In this study, an RGD reverse sequence dGR was conjugated to a CPP octa-arginine to form a CendR (R/KXXR/K) motif contained tandem peptide R8-dGR (RRRRRRRRdGR) which could bind to both integrin αvβ3 and neuropilin-1 receptors. The dual receptor recognizing peptide R8-dGR displayed increased cellular uptake and efficient penetration ability into glioma spheroids in vitro. The following in vivo studies indicated the active targeting and intratumoral diffusion capabilities of R8-dGR modified liposomes. When paclitaxel was loaded in the liposomes, PTX-R8-dGR-Lip induced the strongest anti-proliferation effect on both tumor cells and cancer stem cells, and inhibited the formation of vasculogenic mimicry channels in vitro. Finally, the R8-dGR liposomal drug delivery system prolonged the medium survival time of intracranial C6 bearing mice by 2.1-fold compared to the untreated group, and achieved an exhaustive anti-glioma therapy including anti-tumor cells, anti-vasculogenic mimicry and anti-brain cancer stem cells. To sum up, all the results demonstrated that R8-dGR was an ideal dual receptor recognizing CPP with selective glioma targeting and efficient intratumoral diffusion, which could be further used to equip drug delivery system for effective glioma therapy.

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“…In human airways, resident airway epithelial cells produce pro‐inflammatory mediators under the regulation of PKCδ, which increases NF‐κB‐dependent pro‐inflammatory cytokine generation. PKCα, PKCδ, and PKCϵ have reportedly been involved in the regulation of fibrosis in human pulmonary interstitial fibroblasts . PKC may play a critical role in mediating pulmonary inflammation diseases.…”

Section: Discussionmentioning

confidence: 99%

Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF–PKC pathway

Jiang

Qin

Han

2015

Molecular Carcinogenesis

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The lung is one of the most frequent target organs for breast cancer metastasis. When breast cancer cells from a primary tumor do not colonize the lung, which we named the premetastatic phase, the microenvironment of the lung has already been influenced by the primary tumor. However, little is known about the exact premetastatic alteration and regulatory mechanisms of the lung. Here, we used 4T1 cells (a mouse breast cancer cell line which can specifically metastasize to the lung) to build a mouse breast cancer model. We found that primary breast tumor induced increased pulmonary vascular permeability in the premetastatic phase, which facilitated the leakage of rhodamine-dextran and the extravasation of intravenous therapy injected cancer cells. Furthermore, tight junctions (TJs) were disrupted, and the expression of zonula occludens-1(ZO-1), one of the most important components of tight junctions, was decreased in the premetastatic lung. In addition, elevated serum vascular endothelial growth factor (VEGF) was involved in the destabilization of tight junctions and the VEGF antagonist bevacizumab reversed the primary tumor-induced vascular hyperpermeability. Moreover, activation of the protein kinase C (PKC) pathway disrupted the integrity of TJs and accordingly, the disruption could be alleviated by blocking VEGF. Taken together, these data demonstrate that primary breast cancer may induce tight junction disruptions in the premetastatic lung via the VEGF-PKC pathway and promote pulmonary vascular hyperpermeability before metastasis. © 2015 Wiley Periodicals, Inc.

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Heparin binding VEGF isoforms attenuate hyperoxic embryonic lung growth retardation via a FLK1-neuropilin-1-PKC dependent pathway

Cited by 8 publications

References 42 publications

VEGF-B Is an Autocrine Gliotrophic Factor for Müller Cells under Pathologic Conditions

VEGF-B Is an Autocrine Gliotrophic Factor for Müller Cells under Pathologic Conditions

Dual Receptor Recognizing Cell Penetrating Peptide for Selective Targeting, Efficient Intratumoral Diffusion and Synthesized Anti-Glioma Therapy

Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF–PKC pathway

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