Brain‐specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor

Jeong, Byung Chul; Kim, Miyoung; Lee, Ji Hee; Kee, Hae Jin; Kho, Dhong Hyo; Han, Kae Eun; Qian, Yong; Kim, Jong Keun; Kim, Kyung Keun

doi:10.1016/j.febslet.2005.12.086

Cited by 31 publications

(28 citation statements)

References 19 publications

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“…Decreased VEGF and Robo4 expression after GABPa/ b gene transfer in conjunctival epithelial cells GABPa/b was reported to act both as a transcriptional repressor of VEGF expression in SH-SY5Y and CV-1 cells 21 and as an activator with SP1 of the human Robo4 promoter in primary endothelial cells. 23 We chose human Chang conjunctival epithelial cells to test the expression of the GABPa/b gene in the conjunctiva and cornea by transiently transfecting these cells with increasing doses of lipoplexes carrying a plasmid encoding for the human GABPa and GABPb (GABPa/b) genes.…”

Section: Resultsmentioning

confidence: 99%

“…16 In the present study, we examined the possibility that subconjunctival delivery of the GABP transcription factor to neovascularized cornea could affect the expression patterns of VEGF and Robo4, which were reported to be transcriptionally regulated by GABP and to be critical regulatory proteins in pathologic angiogenesis. 21,23,25,26 Using this approach, we observed for the first time that GABP could delay new vessel formation in a mouse neovascularized cornea for up to 2 weeks after subconjunctival injection of lipoplexes carrying the GABPa/b plasmid DNA adjacent to the corneal neovascular area. We found that gene delivery of the GABPa/b plasmid DNA reduced VEGF and Robo4 expression in conjunctival epithelial cells and in mouse neovascularized cornea, and that GABPa/b-injected cornea had significantly less neovascular area and fewer vessels than did the emptyvector-treated or experimental control groups.…”

Section: Discussionmentioning

confidence: 97%

“…Cell lysates were prepared, resolved by SDS-polyacrylamide gel electrophoresis, transferred and blotted with anti-VEGF (NeoMarkers, Fremont, CA, USA) as described. 21 Total RNAs were prepared from cultured cells or excised pooled corneas. Total RNA (400 ng) was reversetranscribed, as described elsewhere, 16 with random primers and MMLV by the use of RT-PCR kit (Invitrogen, Carlsbad, CA, USA).…”

Section: Plasmids Cell Culture and Rt-pcrmentioning

confidence: 99%

“…17 Recently, we found that the heteromeric complex of GABP (GABPa/b) acts as a transcriptional repressor and thereby inhibits VEGF expression in SH-SY5Y neuroblastoma and green monkey kidney epithelial (CV-1) cells. 21 This suggested testing the possibility of using GABP to control neovascularization of the ocular surface. Ectopic expression of GABP has been reported to induce quiescent cells to reenter the cell cycle, which suggests that GABP is necessary and sufficient for reentry into the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

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Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model

et al. 2009

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Corneal neovascularization can reduce visual acuity. GAbinding protein (GABP) is a transcription factor that regulates the expression of target genes including vascular endothelial growth factor (VEGF) and roundabout4 (Robo4), which participate in pathologic angiogenesis. We assessed whether intraocular injection of the GABP gene affects the growth of new corneal blood vessels in a mouse ocular neovascularization model. Transfection of human GABPa and GABPb gene (GABPa/b) into human conjunctival epithelial cells resulted in decreased VEGF and Robo4 expression. Three groups of mice underwent chemical and mechanical denudation of the corneal epithelium. Subsequently, two groups were administered subconjunctival injection of lipoplexes carrying plasmid DNA encoding for human GABPa/b or an empty plasmid DNA at 1-week intervals. The third group served as an experimental control. In vivo delivery of human GABPa/b into mouse neovascularized cornea reduced VEGF and Robo4 gene expression. Biomicroscopic examination showed that, at 1 week after one or two injections, GABPa/b-treated eyes had significantly less neovascularized corneal area than did eyes treated with the empty vector. Histologic examination showed significantly less vascularized area and fewer blood vessels in the GABP-treated group at 1 week after injections. However, these angiosuppressive effects were weakened at 2 weeks after injections. Our results indicate that subconjunctival GABP gene delivery delays corneal neovascularization for up to 2 weeks in a mouse model of deliberate corneal injury.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Plasmids Cell Culture and Rt-pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model

et al. 2009

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“…The antiangiogenic activity of BAI1 is thought to be mediated by a fragment of its N-terminal extracellular sequence, a fragment known as vasculostatin (17,23,24). BAI2 and BAI3 expression are not p53-inducible, but both proteins also act as inhibitors of angiogenesis (11,14,15,25). Moreover, BAI1 functions as a surface receptor for phosphatidylserine that is exposed on the surface of apoptotic cells, suggesting that BAI1 is an engulfment receptor that can initiate phagocytosis (26).…”

mentioning

confidence: 99%

The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins

Bolliger¹,

Martinelli²,

Südhof

2011

Proc. Natl. Acad. Sci. U.S.A.

161

168

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C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but whose ligands have thus far escaped identification. Using a biochemical approach, we show that all four C1ql proteins bind to the extracellular thrombospondin-repeat domain of BAI3 with high affinity, and that this binding is mediated by the globular C1q domains of the C1ql proteins. Moreover, we demonstrate that addition of submicromolar concentrations of C1ql proteins to cultured neurons causes a significant decrease in synapse density, and that this decrease was prevented by simultaneous addition of the thrombospondin-repeat fragment of BAI3, which binds to C1ql proteins. Our data suggest that C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance.

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Versatile Signaling Activity of Adhesion GPCRs

Kishore

Hall

2016

Adhesion G Protein-Coupled Receptors

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The adhesion G protein-coupled receptors (aGPCRs) are a family of 33 receptors in humans that are widely expressed in various tissues and involved in many diverse biological processes. These receptors possess extremely large N-termini (NT) containing a variety of adhesion domains. A distinguishing feature of these receptors is the presence within the NT of a highly conserved GPCR autoproteolysis-inducing (GAIN) domain, which mediates autoproteolysis of the receptors into N-terminal and C-terminal fragments that stay non-covalently associated. The downstream signaling pathways and G protein-coupling preferences of many aGPCRs have recently been elucidated, and putative endogenous ligands for some aGPCRs have also been discovered and characterized in recent years. A pivotal observation for aGPCRs has been that deletion or removal of the NT up the point of GAIN cleavage results in constitutive receptor activation. For at least some aGPCRs, this activation is dependent on the unmasking of specific agonistic peptide sequences within the N-terminal stalk region (i.e., the region between the site of GAIN domain cleavage and the first transmembrane domain). However, the specific peptide sequences involved and the overall importance of the stalk region for activation can vary greatly from receptor to receptor. An emerging theme of work in this area is that aGPCRs are capable of versatile signaling activity that may be fine-tuned to suit the specific physiological roles played by the various members of this family.

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Brain‐specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor

Cited by 31 publications

References 19 publications

Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model

Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model

The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins

Versatile Signaling Activity of Adhesion GPCRs

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