Rescue of Diabetes-related Impairment of Angiogenesis by Gene Silencing of Thioredoxin-interacting Protein

Dunn, Louise; Buckle, Andrew; Ng, M.

doi:10.1016/j.hlc.2008.05.005

Cited by 2 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TXNIP has been established to regulate the cellular redox state by binding to and inhibiting TRX. Although increasing evidence that cellular redox homeostasis can be an important regulator of angiogenesis (18), the role of TXNIP in mediating VEGF angiogenic signal is not fully understood. The present study documents the first in vivo evidence for redox-dependent mechanisms of TXNIP in modulating VEGF angiogenic signal rather than VEGF expression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thioredoxin-Interacting Protein Expression Is Required for VEGF-Mediated Angiogenic Signal in Endothelial Cells

Abdelsaid

Matragoon

El-Remessy

2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: Thioredoxin-interacting protein (TXNIP) contributes to cellular redox-state homeostasis via binding and inhibiting thioredoxin (TRX). Increasing evidence suggests that cellular redox homeostasis regulates vascular endothelial growth factor (VEGF)-mediated signaling. This study aims to examine the redox-dependant role of TXNIP in regulating VEGF-mediated S-glutathionylation and angiogenic signaling. TXNIP-knockout mice (TKO) or wild-type (WT) treated with the reduced glutathione (GSH)-precursor, N-acetyl cysteine (WT-NAC, 500 mg/kg) were compared to WT using hypoxia-induced neovascularization model. Results: In response to hypoxia, retinas from TKO and WT-NAC mice showed significant decreases in reparative revascularization and pathological neovascularization with similar VEGF expression compared with WT. VEGF failed to stimulate vascular sprouting from aortic rings of TKO compared to WT mice. TKO mice or WT+NAC experienced reductive stress as indicated by twofold increase in TRX reductase activity and fourfold increase in reduced-GSH levels compared with WT. In human microvascular endothelial (HME) cells, VEGF stimulated co-precipitation between vascular endothelial growth factor receptor 2 (VEGFR2) with low molecular weight protein tyrosine phosphatase (LMW-PTP). Silencing TXNIP expression blunted VEGF-induced oxidation of GSH and S-glutathionylation of the LMW-PTP in HME cells. These effects were associated with impaired VEGFR2 phosphorylation that culminated in inhibiting cell migration and tube formation. Overexpression of TXNIP restored VEGFR2 phosphorylation and cell migration in TKO-endothelial cells. Innovation: TXNIP expression is required for VEGF-mediated VEGFR2 activation and angiogenic response in vivo and in vitro. TXNIP expression regulates VEGFR-2 phosphorylation via S-glutathionylation of LMW-PTP in endothelial cells. Conclusion: Our results provide novel mechanistic insight into modulating TXNIP expression as a potential therapeutic target in diseases characterized by aberrant angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The crosstalk between the two systems, as indicated by the ratio of the oxidized to reduced glutathione (GSSG/GSH) reflects antioxidant capacity of the cell (18,19). Shifting redox state to more GSSG reflects a state of oxidative stress, while shifting to more GSH reflects a state of reductive stress.…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin-Interacting Protein Expression Is Required for VEGF-Mediated Angiogenic Signal in Endothelial Cells

Abdelsaid

Matragoon

El-Remessy

2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…Recently, Dunn et al studied the hyperglycemic modulation of TXNIP and Trx proteins in diabetic mice subjected to HLI. Their results show that knockout of TXNIP reduced the deleterious effect of hyperglycemia and improved angiogenesis (Dunn et al 2009;Dunn et al 2010). Furthermore, it D r a f t was revealed that Trx1 overexpressed transgenic (Trx-1 Tg+ ) mice show improved revascularization and decreased fibrosis following femoral artery ligation compared to WT mice (Thirunavukkarasu et al 2014).…”

Section: Thioredoxin Systemmentioning

confidence: 99%

Trimodal rescue of hind limb ischemia with growth factors, cells, and nanocarriers: fundamentals to clinical trials

Lakshmanan

Ukani

Rishi

et al. 2017

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Peripheral artery disease is a severe medical condition commonly characterized by critical or acute limb ischemia. Gradual accumulation of thrombotic plaques in peripheral arteries of the lower limb may lead to intermittent claudication or ischemia in muscle tissue. Ischemic muscle tissue with lesions may become infected, resulting in a non-healing wound. Stable progression of the non-healing wound associated with severe ischemia might lead to functional deterioration of the limb, which, depending on the severity, can result in amputation. Immediate rescue of ischemic muscles through revascularization strategies is considered the gold standard to treat critical limb ischemia. Growth factors offer multiple levels of protection in revascularization of ischemic tissue. In this review, the basic mechanism through which growth factors exert their beneficial properties to rescue the ischemic limb is extensively discussed. Moreover, clinical trials based on growth factor and stem cell therapy to treat critical limb ischemia are considered. The clinical utility of stem cell therapy for the treatment of limb ischemia is explained and recent advances in nanocarrier technology for selective growth factor and stem cell supplementation are summarized.

show abstract

Rescue of Diabetes-related Impairment of Angiogenesis by Gene Silencing of Thioredoxin-interacting Protein

Cited by 2 publications

References 0 publications

Thioredoxin-Interacting Protein Expression Is Required for VEGF-Mediated Angiogenic Signal in Endothelial Cells

Thioredoxin-Interacting Protein Expression Is Required for VEGF-Mediated Angiogenic Signal in Endothelial Cells

Trimodal rescue of hind limb ischemia with growth factors, cells, and nanocarriers: fundamentals to clinical trials

Contact Info

Product

Resources

About