Sonic Hedgehog Induces Notch Target Gene Expression in Vascular Smooth Muscle Cells via VEGF-A

Morrow, David; Cullen, John P.; Liu, Weimin; Guha, Shaunta; Sweeney, Cheryl; Birney, Yvonne A.; Collins, Nora; Walls, Dermot; Redmond, Eileen M.; Cahill, Paul A.

doi:10.1161/atvbaha.109.186890

Cited by 69 publications

(95 citation statements)

References 45 publications

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“…This finding reveals a new effect of Shh on SMCs, in addition to its previously demonstrated role in proliferation of these cells. [16][17][18] Even if Hh proteins are suggested to act on angiogenesis only indirectly, 12,31,32 ECs were shown to respond to Shh by increasing their migration and the impermeability of the brain endothelium. 33 In the context of growing vessels, SMC-derived Shh may not only act on SMCs themselves, but also on the neighborhood ECs by stimulating their migration and consequently by promoting vessel growth.…”

Section: Discussionmentioning

confidence: 99%

“…Because blocking the Hh signaling pathway was well shown to inhibit SMC proliferation in vitro, [16][17][18] the effect of Shh on MC recruitment in vivo may be the result of its effect on MC proliferation instead of migration. However, our data show that in the cornea early steps of new vessel formation do not involve either EC or MC proliferation and moreover that blocking the Hh signaling pathway does not reduce cell proliferation on preexisting limbal vessels, thus suggesting that inhibition of MC proliferation is probably not the target of Hh inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Because Shh was previously shown to promote SMC proliferation in vitro [16][17][18] and to drive the proliferative effect of PDGF-BB, 20 we checked the role of the Hh pathway in NG2…”

Section: Early Recruitment Of Ng2mentioning

confidence: 99%

“…14 Moreover, Shh was shown to upregulate MC-related markers during the formation of microvessel-like structures in vitro 15 suggesting a potential action of Shh in vessel maturation. At the cellular level, recombinant Shh was shown to induce SMC and pericyte proliferation and survival [16][17][18][19] and to contribute to PDGF-BB-induced myofibroblast proliferation. 20 Even though Shh was shown to induce the migration of various cell types such as fibroblasts, 21 ECs, 22 endothelial progenitors, 23 and monocytes, 24 its role and mechanism in SMC migration in vitro and in MC recruitment in vivo have never been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Sonic hedgehog mediates a novel pathway of PDGF-BB–dependent vessel maturation

Yao

Renault

Chapouly

et al. 2014

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Because Shh was previously shown to promote SMC proliferation in vitro [16][17][18] and to drive the proliferative effect of PDGF-BB, 20 we checked the role of the Hh pathway in NG2…”

Section: Early Recruitment Of Ng2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sonic hedgehog mediates a novel pathway of PDGF-BB–dependent vessel maturation

Yao

Renault

Chapouly

et al. 2014

Blood

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“…FIH serves as an asparagine hydroxylase not only for HIF1, but also for Notch ICDs, with the exception of Notch4 ICD, as discussed in the previous section These examples illustrate that the signaling networks between Notch and other pathways are complex and that they are built on compound interactions between signaling pathways at multiple levels. The intersections are not only confined to Wnt, TGF/BMP and hypoxia, but are also elucidated for other pathways, such as the Shh pathway (Driver et al, 2008; Liu et al, 2003;Molnar et al, 2011;Morrow et al, 2009;Mukherjee et al, 2005) and NF-B signaling (for a review, see Poellinger and Lendahl, 2008). A critical node of interaction with other signaling pathways appears to be the Notch ICD, but in some cases independent of any interaction with CSL.…”

mentioning

confidence: 99%

Notch signaling: simplicity in design, versatility in function

2011

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Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.Key words: Cis-inhibition, Delta-like, Signaling diversity, Jagged, Notch, Notch intracellular domain Introduction Cells need to sense cues from their extracellular environment and integrate this information into appropriate developmental or physiological responses. Although there are a number of mechanisms that relay information from the exterior of the cell to the interior, a relatively small set of highly evolutionarily conserved signaling pathways stand out as playing particularly crucial roles in this transmission of information. In this roster of 'elite' intracellular signaling mechanisms are the Wnt pathway, the sonic hedgehog (Shh) pathway, the bone morphogenetic protein/transforming growth factor  (BMP/TGF) pathway, phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and, the subject of this review, the Notch signaling pathway. Each of these pathways converts information about the concentration of extracellular ligands into specific transcriptional responses in the nucleus. In most cases, the signaling mechanism consists of the 'core' signaling pathway, i.e. the minimal set of protein components required for transducing the signal, and a more elaborate set of 'auxiliary' proteins, which, in various ways, impinge upon the core pathway and modify the signal but are not intrinsically necessary for relaying the signal.Among these highly conserved pathways (Gazave et al., 2009;Richards and Degnan, 2009), the Notch signaling pathway scores highly with regard to simplicity in molecular design, as it contains only a small number of core signaling components (Fig. 1). Despite this, Notch signaling affects cell differentiation decisions not only across a wide spectrum of metazoan species, but also across a broad range of cell types in a single organism and at different steps during cell lineage progression. The pleiotropic actions of Notch in different cell types and organs have recently been reviewed and are summarized in Table 1. In keeping with its important role in many cell types, the mutation of Notch genes leads to diseases in various organs and tissues (Table 2). These studies highlight the fact that the Notch pathway must be able to elicit appropriate responses in many spatially and temporally...

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Pathogenetic Mechanisms in Alagille Syndrome

Guha¹,

Walls²,

Redmond³

et al. 2010

Encyclopedia of Life Sciences

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Alagille syndrome (AGS), also known as arteriohepatic dysplasia, is an autosomal dominant disorder characterised by a paucity of interlobular bile ducts and chronic cholestasis, cardiac and vascular dysfunction, skeletal and ocular abnormalities and a characteristic facial appearance. Most cases of AGS in patients harbour mutations in either the JAGGED‐1 ( JAG1 ) or Notch2 receptor ( NOTCH2 ) gene. The JAG1 gene encodes a ligand for the Notch receptor. The Notch signalling network controls mammalian cell fate during embryonic development and also dictates several cell phenotypes in adult cells. The majority of JAG1 mutations seen in AGS patients are null alleles, suggesting JAG1 haploinsufficiency as a primary cause of this disorder. Key Concepts: Alagille syndrome is an autosomal dominant disorder with variable expression. Alagille syndrome and associated abnormalities include those of the liver, heart, eye, skeleton and kidneys and characteristic facial features. Mild‐to‐moderate mental retardation also may be present. Alagille syndrome is most often caused by a mutation, or defect, in the JAGGED1 (JAG1) or NOTCH2 receptor gene. Alagille syndrome has been mapped to the 20p12‐jagged‐1 locus, JAG1, which encodes a ligand critical to the NOTCH gene–signalling cascade that is important in fetal development. Notch signalling has been found to regulate formation of three‐dimensional intrahepatic biliary architecture in murine models and vascular cell phenotype during development. A minority (6–7%) of patients have complete deletion of JAG1, and approximately 15–50% of mutations are spontaneous. Deaths in people with Alagille syndrome are most often caused by liver failure, heart problems and blood vessel abnormalities.

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Sonic Hedgehog Induces Notch Target Gene Expression in Vascular Smooth Muscle Cells via VEGF-A

Cited by 69 publications

References 45 publications

Sonic hedgehog mediates a novel pathway of PDGF-BB–dependent vessel maturation

Sonic hedgehog mediates a novel pathway of PDGF-BB–dependent vessel maturation

Notch signaling: simplicity in design, versatility in function

Pathogenetic Mechanisms in Alagille Syndrome

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