Phorbol esters induce <scp>PLVAP</scp> expression via <scp>VEGF</scp> and additional secreted molecules in <scp>MEK</scp>1‐dependent and p38, <scp>JNK</scp> and <scp>PI</scp>3K/Akt‐independent manner

Hamilton, Byron B.; Tse, Dan; Stan, Radu V.

doi:10.1111/jcmm.13993

Cited by 14 publications

(21 citation statements)

References 46 publications

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“…Inhibition of both TGFβ and VEGF signaling pathways, but not of either of them alone, causes regression of choroid plexus vascular fenestrations (Maharaj et al, 2008). Moreover, VEGF plays a major role in induction of endothelial fenestrations and in maintaining their integrity in mature tissues (Hamilton et al, 2019;Kamba et al, 2006;Stan, 2007). However, it is currently unclear why comparable levels of VEGF and TGFβ induce fenestrae formation only in some vasculatures but not in others, which are often adjacent.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the increased density of fenestrae in plvapb −/− mutant may imply the existence of a Plvapdependent feedback mechanism, in which lower levels of Plvap protein activate an endothelial signaling cascade that drives fenestrae formation. Such a feedback mechanism may involve Vegf signaling, which is known to be crucial for fenestrae formation (Hamilton et al, 2019;Kamba et al, 2006;Stan, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Fenestral diaphragms consist of PLVAP homodimers, the C termini of which form the central density of the diaphragm (reviewed by Stan et al, 1999). In addition to its presence in the diaphragms of endothelial fenestrae, PLVAP is also localized in stomatal diaphragms of caveolae, as well as in transendothelial channels and endothelial pockets (Hamilton et al, 2019;Milici et al, 1986;Stan, 2005;Stan et al, 1999Stan et al, , 2004. Caveolae, which are subcellular pits of the plasma membrane of regular shape and size (50-100 nm), are found in endothelial and other cell types, and are known to be involved in transcytosis (reviewed by Filippini et al, 2018;Stan, 2005).…”

Section: Introductionmentioning

confidence: 99%

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The fenestrae-associated protein Plvap regulates the rate of blood-borne protein passage into the hypophysis

et al. 2019

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To maintain body homeostasis, endocrine systems must detect and integrate blood-borne peripheral signals. This is mediated by fenestrae, specialized permeable pores in the endothelial membrane. Plasmalemma vesicle-associated protein (Plvap) is located in the fenestral diaphragm and is thought to play a role in the passage of proteins through the fenestrae. However, this suggested function has yet to be demonstrated directly. We studied the development of fenestrated capillaries in the hypophysis, a major neuroendocrine interface between the blood and brain. Using a transgenic biosensor to visualize the vascular excretion of the genetically tagged plasma protein DBP-EGFP, we show that the developmental acquisition of vascular permeability coincides with differential expression of zebrafish plvap orthologs in the hypophysis versus brain. Ultrastructural analysis revealed that plvapb mutants display deficiencies in fenestral diaphragms and increased density of hypophyseal fenestrae. Measurements of DBP-EGFP extravasation in plvapb mutants provided direct proof that Plvap limits the rate of blood-borne protein passage through fenestrated endothelia. We present the regulatory role of Plvap in the development of blood-borne protein detection machinery at a neuroendocrine interface through which hormones are released to the general circulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The fenestrae-associated protein Plvap regulates the rate of blood-borne protein passage into the hypophysis

et al. 2019

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“…Moreover, VEGF plays a major role in induction of endothelial fenestrations and in maintaining their integrity in mature tissues (Hamilton et al, 2019;Kamba et al, 2006;Stan, 2007). However, it is currently unclear why comparable levels of VEGF and TGFβ induce fenestrae formation only in some vasculatures but not in others, which are often adjacent.…”

Section: Discussionmentioning

confidence: 99%

Fenestrae-associated protein Plvap regulates the rate of blood-borne proteins passage into the hypophysis

Gordon

Blechman

Shimoni

et al. 2019

Preprint

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To maintain body homeostasis, endocrine systems must detect and integrate a multitude of blood-borne peripheral signals. This is mediated by specialized permeable pores in the endothelial membrane, dubbed fenestrae. Plasmalemma vesicles-associated protein (Plvap) is located in the fenestral diaphragm and is thought play a role in the selective passage of proteins through the fenestrae. However, this suggested function has yet to be demonstrated directly.Here, we studied the development of fenestrated capillaries in a major neuroendocrine interface between the blood and brain, namely the hypophysis. Using a transgenic permeability biosensor to visualize the vascular excretion of a genetically tagged plasma protein (DBP-EGFP), we show that the developmental acquisition of vascular permeability is associated with differential expression of zebrafish plvap orthologs in the hypophysis versus brain.Ultrastructural analysis of the hypophyseal vasculature revealed that plvapb mutants display deficiencies in fenestral and stomatal diaphragms as well as increased density of fenestrae, but not of caveolae. Measurements of DBP-EGFP dynamics in live plvapb mutant larvae provided a direct proof that Plvap limits the rate of blood-borne protein passage through fenestrated endothelia. Overall, we present the regulatory role of Plvap in the development of blood-borne protein detection machinery in a major neuroendocrine interface between the brain and the general circulation.

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“…MCAM is expressed in many tumors and is correlated with cancer progression and metastasis (29). PLVAP is the only known component of the diaphragm that is necessary for diaphragmatic muscle formation (30). PLVAP has been associated with cancer, traumatic spinal cord injury, acute ischemic encephalopathy, graft glomerulopathy, Norrie disease, and diabetic retinopathy (31).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis reveals biomarkers with cancer stem cell characteristics in kidney renal clear cell carcinoma

Zhang¹,

Xiong²,

Zhang³

et al. 2021

Transl Androl Urol

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Background: Kidney renal clear cell carcinoma (KIRC) is a renal cortical tumor. KIRC is the most common subtype of kidney cancer, accounting for 70-80% of kidney cancer. Early identification of the risk of KIRC patients can facilitate more accurate clinical treatment, but there is a lack of effective prognostic markers. We aimed to identify new prognostic biomarkers for KIRC on the basis of the cancer stem cell (CSC) theory.Methods: RNA-sequencing (RNA-seq) data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was used to identify significant modules and hub genes, and predictive hub genes were used to construct prognostic characteristics. Results:The messenger RNA expression-based stemness index (mRNAsi) in tumor tissues of patients in the TCGA database is higher than that of the corresponding normal tissues. In addition, some clinical features and results are highly correlated with mRNAsi. WGCNA found that the green module is the most prominent module associated with mRNAsi; the genes in the green module are mainly concentration in Notch binding, endothelial cell development, Notch signaling pathway, and Rap 1 signaling pathway. A protein-protein interaction (PPI) network showed that the top 10 central genes were significantly associated with the transcriptional level. Moreover, the 10 hub genes were up-regulated in KIRC. Regarding survival analysis, the nomogram of the prognostic markers of the seven pivotal genes showed a higher predictive value. The classical receiver operating characteristic (ROC) curve analysis showed that risk score biomarkers had the highest accuracy and specificity with an area under the curve (AUC) value of 0.701. Conclusions: mRNAsi-related genes may be good prognostic biomarkers for KIRC.

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Phorbol esters induce PLVAP expression via VEGF and additional secreted molecules in MEK1‐dependent and p38, JNK and PI3K/Akt‐independent manner

Cited by 14 publications

References 46 publications

The fenestrae-associated protein Plvap regulates the rate of blood-borne protein passage into the hypophysis

The fenestrae-associated protein Plvap regulates the rate of blood-borne protein passage into the hypophysis

Fenestrae-associated protein Plvap regulates the rate of blood-borne proteins passage into the hypophysis

Bioinformatics analysis reveals biomarkers with cancer stem cell characteristics in kidney renal clear cell carcinoma

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