Hypoxia-Inducible Factor-1-Dependent and -Independent Regulation of Insulin-Like Growth Factor-1-Stimulated Vascular Endothelial Growth Factor Secretion

Slomiany, Mark G.; Rosenzweig, Steven A

doi:10.1124/jpet.106.104158

Cited by 64 publications

(52 citation statements)

References 38 publications

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“…While tumor cells express VEGF necessary for the chemotaxis of endothelial cells into the growing tumor tissue, the process of wound angiogenesis is dependent on endogenously expressed VEGF produced by various cells, including macrophages and keratinocytes [13,27]. Thus, inactivation of Akt causes inhibition of VEGF expression as has been reported by several groups [29,33,38,41]. In turn, reduced VEGF levels seem to be responsible for defective angiogenesis in wounds of Akt1 -/-mice.…”

Section: Discussionmentioning

confidence: 80%

Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing

2008

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Previous in vivo and in vitro studies have shown that Akt1 serves as a crucial regulator of vascular maturation, extracellular matrix composition, and angiogenesis in tumors. Hence, we hypothesized that Akt1 may be necessary for other angiogenesis-dependent processes, including wound healing. Using Akt1 -/-and Akt2 -/-mice, we demonstrate that deficiency of Akt1, but not Akt2, results in impaired assembly of collagen in skin wounds and around the blood vessels. Wounds in Akt1 -/-mice, but not in Akt2 -/-mice, were characterized by reduced vascular area as well as impaired vascular maturation as evidenced by reduced smooth muscle cell recruitment. Expression level of a major angiogenic growth factor, VEGF, was significantly lower in wound tissues of Akt1 -/-mice as compared to WT. However, despite the impaired collagen assembly and reduced angiogenesis in Akt1 -/-wounds, no significant difference in migration of fibroblasts into the wound area was observed between WT and Akt1 -/-mice. Importantly, the dynamics of wound closure were similar between WT, Akt1 -/-, and Akt2 -/-mice. Thus, it appears that although the lack of Akt1 impairs VEGF expression, wound angiogenesis, and subsequent maturation of vasculature, it has no effect on the wound closure. These findings may have clinical applications for the improvement of treatment procedures with reported history of wound healing complications.

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Section: Discussionmentioning

confidence: 80%

Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing

2008

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“…Recently, however, Mark et al reported that IGF-I treatment led to increased HIF-1α mRNA levels in the retinal pigment epithelium (RPE) cells ARPE-19 [5] . In the present study, IGF-I did not obviously up-regulate HIF-1α mRNA levels in MCF-7 cells ( Figure 2C).…”

Section: Discussionmentioning

confidence: 99%

“…We wondered whether the tube formation was induced by IGF-I directly or by other genes. Previous studies have demonstrated that IGF-I can enhance the expression of VEGF [5][6][7][8] , which plays a central role in the process of angiogenesis. Our results also showed that IGF-I induced VEGF expression and transcriptional activation (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

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Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Tang

Zhou

2009

Acta Pharmacol Sin

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“…As discussed in detail above, IGFs promote endothelial cell migration and tube formation in vitro. IGF1 and IGF2 stimulate HIF1A expression (Hoeben et al 2004), and IGF1 induces VEGF synthesis (Warren et al 1996, Stearns et al 2005) via HIF1-dependent andindependent pathways (Slomiany & Rosenzweig 2006). IGF2 also plays a role in angiogenesis (Wang et al 1998, Kim et al 2012, at least in part by inducing VEGF synthesis (Hoeben et al 2004 IGFs are involved in early vascular development.…”

Section: Insulin-like Growth Factorsmentioning

confidence: 99%

Endothelial cells and the IGF system

Bach¹

2014

Journal of Molecular Endocrinology

152

118

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Endothelial cells line blood vessels and modulate vascular tone, thrombosis, inflammatory responses and new vessel formation. They are implicated in many disease processes including atherosclerosis and cancer. IGFs play a significant role in the physiology of endothelial cells by promoting migration, tube formation and production of the vasodilator nitric oxide. These actions are mediated by the IGF1 and IGF2/mannose 6-phosphate receptors and are modulated by a family of high-affinity IGF binding proteins. IGFs also increase the number and function of endothelial progenitor cells, which may contribute to protection from atherosclerosis. IGFs promote angiogenesis, and dysregulation of the IGF system may contribute to this process in cancer and eye diseases including retinopathy of prematurity and diabetic retinopathy. In some situations, IGF deficiency appears to contribute to endothelial dysfunction, whereas IGF may be deleterious in others. These differences may be due to tissue-specific endothelial cell phenotypes or IGFs having distinct roles in different phases of vascular disease. Further studies are therefore required to delineate the therapeutic potential of IGF system modulation in pathogenic processes.

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Hypoxia-Inducible Factor-1-Dependent and -Independent Regulation of Insulin-Like Growth Factor-1-Stimulated Vascular Endothelial Growth Factor Secretion

Abstract: Hypoxia-induced stress plays a central role in retinal vascular disease and cancer. Increased hypoxia-inducible factor-1␣

Cited by 64 publications

References 38 publications

Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing

Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

Endothelial cells and the IGF system

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