Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7

Wang, Shusheng; Li, Xiumin; Parra, Maribel; Verdin, Eric; Bassel‐Duby, Rhonda; Olson, Eric N.

doi:10.1073/pnas.0802857105

Cited by 222 publications

(209 citation statements)

References 39 publications

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“…Both Egr3 and Nurr77 are required for effective VEGF-mediated migration and tube formation in HUVECs, suggesting that PKD may regulate angiogenic responses in part by mediating transcription of these genes (10,31). HDAC7 also regulates Nurr77 transcription via MEF2, and another gene, RCAN2, which stimulates angiogenesis via the calcineurin-NFAT pathway (29,32). As with HDAC5, HDAC7 phosphorylation and subsequent nuclear export were stimulated by VEGF and mediated by PKD1 (29).…”

Section: Pkd Function In Endothelial Cellsmentioning

confidence: 97%

“…HDAC7 also regulates Nurr77 transcription via MEF2, and another gene, RCAN2, which stimulates angiogenesis via the calcineurin-NFAT pathway (29,32). As with HDAC5, HDAC7 phosphorylation and subsequent nuclear export were stimulated by VEGF and mediated by PKD1 (29). It is possible that other genes are transcriptionally regulated by PKD and these remain to be determined.…”

Section: Pkd Function In Endothelial Cellsmentioning

confidence: 99%

“…In a recent study, CREB dependent transcription of the immediate-early gene, Nurr1, was found to be important for in vivo angiogenesis in a mouse model using matrigel plugs (27). Furthermore, PKD can also phosphorylate several members of the Class IIa histone deacetylase (HDAC) family, notably HDAC5 and HDAC7 (10,28,29). HDACs repress transcription by reducing the level of histone acetylation, whereas phosphorylation of HDACs induces their export from the nucleus, thereby facilitating the transcription of target genes.…”

Section: Pkd Function In Endothelial Cellsmentioning

confidence: 99%

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Protein kinase D in vascular biology and angiogenesis

Evans

Zachary

2011

IUBMB Life

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SummaryThe Protein Kinase D (PKD) family comprises diacylglycerol stimulated serine/threonine protein kinases that participate in many key signaling pathways in a diverse range of cells. Recent studies show that PKD isoforms 1 and 2 play critical roles in vascular biology and angiogenesis and there has been considerable progress in determining some of the key angiogenic signaling pathways mediated by PKD in endothelial cells. Less is currently known regarding the specific roles of PKD isoforms in endothelial cells and the role of PKD in smooth muscle cells. PKD is also emerging as a potentially important mediator of tumor growth and tumor angiogenesis and there is growing interest in PKD as a novel therapeutic target in cancer.

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Section: Pkd Function In Endothelial Cellsmentioning

confidence: 97%

Section: Pkd Function In Endothelial Cellsmentioning

confidence: 99%

Section: Pkd Function In Endothelial Cellsmentioning

confidence: 99%

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Protein kinase D in vascular biology and angiogenesis

Evans

Zachary

2011

IUBMB Life

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“…Migration of kidney pericytes and kidney MVECs was assessed using a scratch wound assay as described 5,37 with some modifications.…”

Section: Migration Assaysmentioning

confidence: 99%

EphrinB2 Reverse Signaling Protects against Capillary Rarefaction and Fibrosis after Kidney Injury

Kida

Ieronimakis

Schrimpf

et al. 2013

Journal of the American Society of Nephrology

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Microvascular disease, a characteristic of acute and chronic kidney diseases, leads to rarefaction of peritubular capillaries (PTCs), promoting secondary ischemic injury, which may be central to disease progression. Bidirectional signaling by EphB4 receptor and ephrinB2 ligand is critical for angiogenesis during murine development, suggesting that ephrinB2 reverse signaling may have a role in renal angiogenesis induced by injury or fibrosis. Here, we found that ephrinB2 reverse signaling is activated in the kidney only after injury. In mice lacking the PDZ intracellular signaling domain of ephrinB2 (ephrinB2 DV), angiogenesis was impaired and kidney injury led to increased PTC rarefaction and fibrosis. EphrinB2 DV primary kidney pericytes migrated more than wild-type pericytes and were less able to stabilize capillary tubes in threedimensional culture and less able to stimulate synthesis of capillary basement membrane. EphrinB2 DV primary kidney microvascular endothelial cells migrated and proliferated less than wild-type microvascular endothelial cells in response to vascular endothelial growth factor A and showed less internalization and activation of vascular endothelial growth factor receptor-2. Taken together, these results suggest that PDZ domain-dependent ephrinB2 reverse signaling protects against PTC rarefaction by regulating angiogenesis and vascular stability during kidney injury. Furthermore, this signaling in kidney pericytes protects against pericyte-to-myofibroblast transition and myofibroblast activation, thereby limiting fibrogenesis.

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“…The signal transduction pathways that are activated in different cell types in response to VEGF are well established (Cross et al, 2003;Wang et al, 2008). However, relatively little is known about the involvement of distinct phosphoinositide 3-kinase (PI3K) catalytic subunits and protein kinase C (PKC) isoforms in VEGF action (Hamada et al, 2005;Gliki et al, 2002;Gerber et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells

Bekhite

Finkensieper

Binas

et al. 2011

Journal of Cell Science

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SummaryVEGF-, phosphoinositide 3-kinase (PI3K)-and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1 + cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110a and p110 using short hairpin RNA (shRNA), or inhibition of p110a with compound 15e and of p110 with IC-87114 impaired cardiac and vascular differentiation. By contrast, TGX-221, an inhibitor of p110b, and shRNA knockdown of p110b were without significant effects. Antagonists of the PKC family, i.e. bisindolylmaleimide-1 (BIM-1), GÖ 6976 (targeting PKCa/bII) and rottlerin (targeting PKC) abolished vasculogenesis, but not cardiomyogenesis. Inhibition of Akt blunted cardiac as well as vascular differentiation. VEGF induced phosphorylation of PKCa/bII and PKC but not PKCz. This was abolished by PI3K inhibitors and the VEGFR-2 antagonist SU5614. Furthermore, phosphorylation of Akt and phosphoinositidedependent kinase-1 (PDK1) was blunted upon inhibition of PI3K, but not upon inhibition of PKC by BIM-1, suggesting that activation of Akt and PDK1 by VEGF required PI3K but not PKC. In summary, we demonstrate that PI3K catalytic subunits p110a and p110 are central to cardiovasculogenesis of ES cells. Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis.

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Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7

Cited by 222 publications

References 39 publications

Protein kinase D in vascular biology and angiogenesis

Protein kinase D in vascular biology and angiogenesis

EphrinB2 Reverse Signaling Protects against Capillary Rarefaction and Fibrosis after Kidney Injury

VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells

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