5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

Wu, Weiqiang; Fauzee, Nilufer Jasmine Selimah; Wang, Yalan

doi:10.7314/apjcp.2012.13.3.991

Cited by 2 publications

(2 citation statements)

References 35 publications

(40 reference statements)

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“…It has been proved that the key pro-lymphangiogenesis molecules include VEGF-C/VEGFR3 signaling (the central regulator) [ 2 , 47 ], inflammatory factors IL-1β and TNF-α [ 48 ], MMPs [ 49 – 51 ], and phosphorylated NF-κB p65 [ 28 , 52 ], etc. Our in vivo experiments show that the above pro-lymphangiogenesis molecules were up-regulated in HMGB1-treatmet ILA corneas and were down-regulated in ILA corneas with Knock-out of TLR4 or antagonizing HMGB1 by A-box.…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

et al. 2016

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Lymphangiogenesis in inflammation has received considerable attention in recent years. Administration of modulating lymphangiogenesis provides more possibilities of treating inflammation-associated diseases. However, the main mediators and factors governing inflammation-induced lymphangiogenesis (ILA) are yet to be defined. Here, we explored the role of HMGB1-TLR4 signalling pathway in modulating inflammation-induced lymphangiogenesis and its underlying mechanisms using an ILA mouse model and 2 cell lines. Our results show that HMGB1 promoted VEGF-C-induced HDLECs proliferation in a dose-dependent manner and TLR4 mediates HMGB1-induced LECs proliferation and tube formation in vitro. And in vivo, rHMGB1 treatment significantly promoted ILA, and the promoting effects was inhibited notably when HMGB1-TLR4 was blocked. HMGB1-associated ILA is primarily dependent on TLR4 but not on TLR2. In mechanisms, the recruitment and activation of CD11b+ cells are important cellular mechanisms in HMGB1-TLR4 associated ILA, and multiple key pro-lymphangiogenesis molecules mediates HMGB1-TLR4 associated ILA, including VEGF-C/VEGFR3, inflammatory factors IL-1β and TNF-α, MMP-2 and MMP-9 and NF-κB p65. In conclusion, HMGB1-associated ILA is primarily dependent on TLR4, and CD11b+ cells and multiple molecular mechanisms mediate HMGB1-TLR4 associated ILA. Furthermore, the ILA can be effectively modulated by HMGB1-TLR4 signalling. Consequently, administration of modulating ILA through HMGB1-TLR4 pathway may provide us more possibilities of treating inflammation and lymphangiogenesis associated diseases.

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Section: Discussionmentioning

confidence: 99%

High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

et al. 2016

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“…The authors proposed that this effect on expression of PARP-1 was due to inhibition of PARP-1 activity, leading to down-regulation of the activity of NF-B. Following on from this initial study, the same group confirmed the effect on the expression of PARP-1 but also observed that the expression of vascular endothelial growth factor-C (VEGF-C) was down-regulated by 1, though inhibition of PARP-1 and down-regulation of NF-B [146]. VEGF-C is involved in angiogenesis, so the authors proposed that PARP-1 may regulate angiogenesis and inhibition thereof with 1 may inhibit this process.…”

Section: -Aiq and Cancermentioning

confidence: 73%

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

Threadgill

2015

CMC

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5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of only moderate potency in vitro against PARP-1, it is highly active in many assays in cells and in models in vivo, indicating excellent uptake. Optimisation of the several synthetic sequences to 5-AIQ has led to development of a short and efficient route from 1-chloroisoquinoline. It has been used widely as a biochemical and pharmacological tool to study the effects of inhibition of the PARPs. It ameliorates the damage to cells and tissues following reperfusion of ischaemic tissue, showing significant protective activity in a rodent model of haemorrhagic shock at the remarkably low dose of 30 µg Kg(-1). Protection is also seen in models of myocardial infarction, ischaemic kidney and liver disorders, stroke and organ transplantation. Inhibition of PARP-1 by 5-AIQ causes down-regulation of the activity of NF-κB, which then down-regulates the expression of several gene products. Thus 5-AIQ has anti-inflammatory activity in vivo, through modulating the expression of cytokines and adhesion molecules. This indirect inhibition of expression is relevant in the activity of 5-AIQ in models of arthritis, Parkinson's disease, multiple sclerosis, spinal cord injury, periodontitis and inflammatory conditions of the lung. Inhibition of expression of matrix metalloproteinases and other factors gives rise to anti-angiogenic activity and to remarkable anti-metastatic activity in a mouse model. Thus, although it has been overtaken by other PARP-inhibiting drugs in the oncological clinic, 5-AIQ remains a valuable tool to study the roles of PARPs in health and in diverse diseases.

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5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

Cited by 2 publications

References 35 publications

High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

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