Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

Guzmán-Hernández, María Luisa; Potter, Gael; Égervári, Kristóf; Kiss, József Zoltán; Balla, Tamás

doi:10.1091/mbc.e13-07-0418

Cited by 29 publications

(37 citation statements)

References 57 publications

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“…Regardless of whether VEGF levels are altered in the serum of women with preeclampsia, local levels within the uterus and placenta are likely more relevant, since VEGF mostly becomes bound to plasma membrane and extracellular matrix after secretion and is widely viewed to function in a paracrine fashion (22)(23)(24). Therefore, we began our studies by determining the localization and relative expression levels of VEGF and sFLT1 at the decidualplacental interface in normal and preeclamptic pregnancies.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, VEGF has been shown to stimulate release of sFLT1 from human placental explants in a dose-dependent manner (12), and VEGF treatment in pregnant mice can induce hypercoagulation and hypertension, some of the clinical manifestations of preeclampsia (21). Given that local VEGF level is a key determinant of VEGF function (22)(23)(24)31), our findings that VEGF levels were increased specifically in the local microenvironment in the decidua and that sFLT1 was specifically increased in nearby trophoblasts in preeclamptic women strongly suggests a role for local VEGF in stimulating sFLT1 production in these cells. Although it is also possible that placental sFLT1 stimulates decidual VEGF expression in preeclampsia, we are not aware of any evidence in the literature to support this supposition.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications

Fan¹,

Rai²,

Kambham³

et al. 2014

J. Clin. Invest.

159

166

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Figure 8. Effects of placental sFlt1 knockdown with or without endometrial VEGF overexpression. (A-L) Placental sFlt1 knockdown. Upon placentaspecific sFLT1 shRNA expression, widespread hemorrhaging in the fetus (B) and at the placental-decidual junction (D) was observed on GD18 compared with controls (A and C). Histological examination of sFLT1 shRNA-expressing placentas revealed extraordinary dilation of some maternal blood sinuses (arrowheads) in the labyrinth (E and F) and fibrin deposition (arrow) in these spaces (G and H). (I and J) MSB staining revealed extravasated fibrin (arrow) in adjacent areas. Placental sFlt1 knockdown did not affect implantation rate (K), whereas the fetal resorption rate significantly increased (L). (M-V) Placental sFlt1 knockdown enhanced the deleterious effects in Endo-VEGF animals. Pregnancies surviving to GD16 exhibited (M) excessive vaginal bleeding and (N-P) termination of pregnancy or resorption (arrows denote resorption sites) as well as (Q) widespread and extensive hemorrhaging in fetuses and placentas (arrowheads) and in deciduas at the maternal-fetal junction (asterisk). Histological examination (R-T) revealed widespread dilation and congestion of maternal blood sinuses (arrowheads) in the labyrinth, venous sinuses, and veins at maternal-fetal junctions, and MSB staining (U and V) demonstrated extensive fibrin extravasation (arrows) in the labyrinth and at the maternal-fetal junction. Results are mean ± SD. *P < 0.05 (n = 15). Scale bars: 2 mm (A-D); 500 μm (E, F, and R); 50 μm (G-J); 100 μm (S-V).

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications

Fan¹,

Rai²,

Kambham³

et al. 2014

J. Clin. Invest.

159

166

View full text Add to dashboard Cite

show abstract

“…Data shown here indicated that, as compared with control microglial cells, these receiving PF pretreatment exhibited weaker migratory capability to Aβ 1-42 ( Figure 6). To determine whether PF-induced blockade of VGEF/Flt-1 axis could affect the microglia chemotactic movement to Aβ 1-42 peptides, VEGF 165 , a major form of VEGF secreted from cells (Guzman-Hernandez et al, 2014), was used to mimic VEGF effects. We noted that restoration of 7 VEGF could overcome the inhibitory effect of PF on Aβ 1-42 -induced microglial chemotaxis ( Figure 6).…”

Section: Pf Inhibits Microglial Chemotaxis Towards Aβ 1-42 Via Inhibimentioning

confidence: 99%

Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways

Liu¹,

Wang

et al. 2015

Brain Research

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“…Previous studies have reported that Arf1 regulates VEGF secretion (21) and controls capillary tubule formation by ECs (22). Among the 15 Arf GEFs encoded in the human genome (40), it remains largely unknown which participate in activation of Arf1 to regulate transport of secreted VEGF.…”

Section: Big1 or Big2 Knockdown In Glioblastoma U251 Cells Diminishesmentioning

confidence: 99%

“…Previous studies indicated that Arf1 plays a role in regulating VEGF signaling. Interference with Arf1 activation led to a significant reduction of VEGF secretion (21), and inhibition of Arf1 expression disrupted VEGFinduced vascular permeability and the in vitro capillary tubule formation (22). However, whether BIG1 and BIG2 regulate VEGF expression and secretion to modulate angiogenesis in ECs and vascular development has not been previously shown.…”

mentioning

confidence: 99%

Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis

Wang

et al. 2019

FASEB j.

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VEGF stimulates the formation of new blood vessels by inducing endothelial cell (EC) proliferation and migration. Brefeldin A (BFA)‐inhibited guanine nucleotide–exchange protein (BIG)1 and 2 accelerate the replacement of bound GDP with GTP to activate ADP‐ribosylation factor (Arf)1, which regulates vesicular transport between the Golgi and plasma membrane. Although it has been reported that treating cells with BFA interferes with Arf1 activation to inhibit VEGF secretion, the role of BIG1 and BIG2 in VEGF trafficking and expression, EC migration and proliferation, and vascular development remains unknown. Here, we found that inactivation of Arf1 reduced VEGF secretion but did not affect the levels of VEGF protein. Interestingly, however, BIG1 and BIG2 knockdown significantly decreased the levels of VEGF mRNA and protein in glioblastoma U251 cells and HUVECs. Furthermore, depletion of BIG1 and BIG2 inhibited HUVEC angiogenesis by diminishing cell migration. Angioblast migration and intersegmental vessel sprouting were also impaired when the BIG2 homolog, Arf guanine nucleotide exchange factor (arfgef)2, was knocked down in zebrafish with endothelial expression of green fluorescent protein (GFP). Depletion of arfgef2 by clustered regularly interspaced short palindromic repeat (CRISPR)/ CRISPR‐associated protein 9 (Cas9) also caused defects in vascular development of zebrafish embryos. Taken together, these data reveal that BIG1 and BIG2 participate in endothelial cell angiogenesis.—Lu, F.‐L, Wang, Y.‐T., Wang, Y.‐S., Wu, C.‐Y., Li, C.‐C. Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis. FASEB J. 33, 9959–9973 (2019). http://www.fasebj.org

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Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

Cited by 29 publications

References 57 publications

Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications

Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications

Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways

Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis

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