Role of TGF-β in Vascular Development and Vascular Reactivity

Perrella, Mark A.; Jain, Mukesh K.; Lee, Mu-En

doi:10.1159/000057361

Cited by 25 publications

(18 citation statements)

References 46 publications

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“…Therefore, induction of Igfbp2 and Prss11 during heterologous growth control may decrease vascularization of tumor cells in vivo. Suppression of tumor vascularization during heterologous growth control is also inferred by activation of the gene encoding endothelin, which can inhibit angiogenesis (44), in concert with suppression of genes encoding proliferin, which increase angiogenesis (45).…”

Section: Discussionmentioning

confidence: 99%

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Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Alexander

Ichikawa²,

Bechberger

et al. 2004

Cancer Research

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The growth of many types of cancer cells can be controlled by surrounding normal cells. However, mechanisms underlying this phenomenon have not been defined. We used a layered culture system to investigate how nontransformed cells suppress the growth of neighboring transformed cells. Direct physical contact between transformed and nontransformed cells was required for growth suppression of transformed cells in this system; communication by diffusible factors was not sufficient. However, significant gap junctional communication was not required, indicating that other intercellular junctions mediated this growth regulatory response. We also report that the Src kinase activity in transformed cells was not directly inhibited by contact with nontransformed cells. Instead, nontransformed cells increased the expression of serum deprivationresponse protein and the transcription factor four and a half LIM domain 1 in tumor cells. In addition, these results suggest mechanisms by which normal cells may block Wnt signaling, inhibit insulin-like growth factor activity, and promote host recognition of neighboring tumor cells.

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Section: Discussionmentioning

confidence: 99%

“…encoding BMP4 (Bmp4) and endothelin (Edn1) were increased over 2-fold. Interestingly, in addition to BMP4 signaling, induction of endothelin may decrease tumor vascularization (44).…”

Section: Mechanisms Of Heterologous Growth Controlmentioning

confidence: 99%

Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Alexander

Ichikawa²,

Bechberger

et al. 2004

Cancer Research

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“…TGF-β signaling plays pivotal roles in SMC differentiation during vascular development as well as phenotypic switching in disease states [52] . The importance of TGF-β signaling pathway in SMC differentiation during embryonic development has been demonstrated by numerous studies [53] . Gene-targeting studies in mice have shown that a loss of TGF-β signaling components generally leads to abnormal differentiation and maturation of the primitive vascular network, resulting in defective vessels losing integrity of the vessel wall.…”

Section: Differentiation During Embryonic Developmentmentioning

confidence: 99%

Transforming growth factor-β and smooth muscle differentiation

Guo¹

2012

WJBC

105

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Transforming growth factor (TGF)-β family members are multifunctional cytokines regulating diverse cellular functions such as growth, adhesion, migration, apoptosis, and differentiation. TGF-βs elicit their effects via specific type Ⅰ and type Ⅱ serine/threonine kinase receptors and intracellular Smad transcription factors. Knockout mouse models for the different components of the TGF-β signaling pathway have revealed their critical roles in smooth muscle cell (SMC) differentiation. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular disorders such as aorta aneurysm and congenital heart diseases due to SMC defects. In this review, the current understanding of TGF-β function in SMC differentiation is highlighted, and the role of TGF-β signaling in SMCrelated diseases is discussed.

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“…TGFb signaling is thought to play a critical role in vascular development and function due to effects on endothelial cell proliferation and migration, fibronectin synthesis and mural cell differentiation (reviewed in Bohnsack and Hirschi, 2004;Perrella et al, 1998). This idea is supported by the fact that embryonic lethality in some Tgfb1 À/À mouse embryos is due to failed yolk sac vasculogenesis (Dickson et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

TGFβ1 and TGFβ3 are partially redundant effectors in brain vascular morphogenesis

Yang

et al. 2008

Mechanisms of Development

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Gene deletion experiments have shown that the three TGFbeta isoforms regulate distinct developmental processes. Recent work by our group and others showed that the integrins alphavbeta6 and alphavbeta8 activate latent forms of TGFbeta1 and TGFbeta3. This raises the possibility that TGFbeta1 and TGFbeta3 act redundantly in developmental processes where both isoforms are expressed and activation is by integrins. To investigate this issue, we generated mice with defective integrin-mediated TGFbeta1 activation (Tgfb1(RGE/RGE)) that were also homozygous for a null mutation in the TGFbeta3 gene. Tgfb1(RGE/RGE); Tgfb3(-/-) mice have severely perturbed development of the brain vasculature that is highly similar to that in mice lacking alphavbeta8. Some Tgfb1(RGE/RGE); Tgfb3(+/-) and Tgfb1(RGE/RGE); Tgfb3(+/+) mice have milder, background-dependent versions of the phenotype. In addition, we found that Tgfb3 gene status influences embryonic lethality due to TGFbeta1 deficiency after limited backcrossing to the BALB/c background. Conversely, Tgfb1 gene status modifies the extent of palate fusion in Tgfb3(-/-) mice after limited backcrossing to the ICR background. Our results are consistent with a functional connection between TGFbeta1 and TGFbeta3 during development based on a shared mechanism of activation.

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Role of TGF-β in Vascular Development and Vascular Reactivity

Cited by 25 publications

References 46 publications

Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Transforming growth factor-β and smooth muscle differentiation

TGFβ1 and TGFβ3 are partially redundant effectors in brain vascular morphogenesis

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