Hepatocyte growth factor stimulated angiogenesis without inflammation: Differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor

Kaga, Toshihiro; Kawano, Hirokazu; Sakaguchi, Makoto; Nakazawa, Takahiro; Taniyama, Yoshiaki; Morishita, Ryuichi

doi:10.1016/j.vph.2012.02.002

Cited by 76 publications

(48 citation statements)

References 18 publications

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“…In agreement with our results, it was previously reported that IL-8 promotes proliferation, tube formation and migration of HUVECs and lymphatic endothelial cells [44,45]. Recent data have shown also that recombinant FGF2 stimulation, in contrast to HGF and VEGF, increases the production of MCP-1 and IL-8 in vascular smooth muscle cells, following the activation of NFjB, a key transcriptional factor of inflammation [46]. Those authors suggest that the expression of proinflammatory factors such as TNF-a, IL-6, IL-8 and MCPs following the activation of NFjB may cause an increase in vascular permeability.…”

Section: Discussionsupporting

confidence: 93%

The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production

et al. 2015

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In recent years, special attention has been paid to finding new pro-angiogenic factors which could be used in gene therapy of vascular diseases such as critical limb ischaemia (CLI). Angiogenesis, the formation of new blood vessels, is a complex process dependent on different cytokines, matrix proteins, growth factors and other pro- or anti-angiogenic stimuli. Numerous lines of evidence suggest that key mediators of angiogenesis, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) together with fibroblast growth factor2 (FGF2) are involved in regulation of the normal and pathological process of angiogenesis. However, less information is available on the complex interactions between these and other angiogenic factors. The aim of this study was to characterise the effect of fibroblast growth factor2 on biological properties of human endothelial progenitor cells with respect to the expression level of other regulatory cytokines. Ectopic expression of FGF2 in EP cells stimulates their pro-angiogenic behaviour, leading to increased proliferation, migration and tube formation abilities. Moreover, we show that the expression profile of VEGF and other pro-angiogenic cytokines, such as HGF, MCP2, and interleukins, is affected differently by FGF2 in EPC. In conclusion, we provide evidence that FGF2 directly affects not only the biological properties of EP cells but also the expression pattern and secretion of numerous chemocytokines. Our results suggest that FGF2 could be applied in therapeutic approaches for CLI and other ischaemic diseases of the vascular system in vivo.

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Section: Discussionsupporting

confidence: 93%

The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production

et al. 2015

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“…Gene expression of FGF-stimulated endothelial cells shows, together with a prominent proangiogenic profile, a proinflammatory signature characterised by the upregulation of proinflammatory cytokines/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway 12. Furthermore, upregulation of FGF was associated with an increase in the vascular permeability 13. Thus, inhibition of FGF signals could constitute a therapeutic strategy for attenuating excessive or chronic inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Chronic cystoid macular oedema treated with intravitreal dobesilate: Figure 1

Cuevas¹,

Outeiriño²,

Angulo³

et al. 2012

BMJ Case Reports

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“…There are two identified elimination mechanisms for HGF: receptor-mediated endocytosis through HGF/cMET, and endocytosis through heparin on the cell surface 70 . However, the use of plasmid DNA delivery of HGF has been and is being successfully used in clinical models 71, 74, 75 . There are also reports of HGF being administered via hydrogels 60, 76, 77 and using small molecule mimetics of HGF 78 to produce positive effects in vitro and in vivo .…”

Section: 2 Therapeutic Implicationsmentioning

confidence: 99%

Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair

Frisch

Curtis

Aenlle

et al. 2016

Expert Opinion on Therapeutic Targets

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Introduction Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. These pluripotent cells secrete hepatocyte growth factor (HGF), which regulates cell growth, survival, motility, migration, mitogenesis and is important for tissue development/regeneration. HGF has four splice variants, NK1, NK2, NK3, and NK4 which have varying functions and affinities for the HGF receptor, cMET. HGF promotes osteoblastic differentiation of MSCs into bone forming cells, playing a role in bone development, health and repair. Areas Covered This review will focus on the effects of HGF in osteogenesis, bone repair and bone health, including structural and functional insights into the role of HGF in the body. Expert Opinion Approximately 6.2 million Americans experience a fracture annually, with 5–10% being mal- or non-union fractures. HGF is important in priming MSCs for osteogenic differentiation in vitro and is currently being studied to assess its role during bone repair in vivo. Due to the high turnover rate of systemic HGF, non-classic modes of HGF-treatment, including naked-plasmid HGF delivery and the use of HGF splice variants (NK1 & NK2) are being studied to find safe and efficacious treatments for bone disorders, such as mal- or non-union fractures.

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Hepatocyte growth factor stimulated angiogenesis without inflammation: Differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor

Cited by 76 publications

References 18 publications

The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production

The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production

Chronic cystoid macular oedema treated with intravitreal dobesilate: Figure 1

Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair

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