IGFBP-3 inhibits TNF-α production and TNFR-2 signaling to protect against Retinal Endothelial Cell Apoptosis

Zhang, Qiuhua; Steinle, Jena J.

doi:10.1016/j.mvr.2014.07.009

Cited by 29 publications

(20 citation statements)

References 41 publications

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“…Transcriptional upregulation of ADAM17 was associated with an increase in ADAM17 protein levels that was also sustained 48 h post high glucose treatment ( Figure 6B). These data are in agreement with findings of others who showed upregulation of ADAM17 enzymatic activity in retinal endothelial cells in high glucose conditions [33].…”

Section: Glucidic Stress Upregulates Expression Of Adam17 In Hrecsupporting

confidence: 94%

Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy

Shalaby

Thounaojam

Tawfik

et al. 2020

JCM

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ADAM17, a disintegrin and metalloproteinase 17, is a transmembrane metalloproteinase that regulates bioavailability of multiple membrane-bound proteins via ectodomain shedding. ADAM17 activity was shown to contribute to a number of vascular pathologies, but its role in the context of diabetic retinopathy (DR) is not determined. We found that expression and enzymatic activity of ADAM17 are upregulated in human diabetic postmortem retinas and a mouse model of streptozotocin-induced diabetes. To further investigate the contribution of ADAM17 to vascular alterations associated with DR, we used human retinal endothelial cells (HREC) treated with ADAM17 neutralizing antibodies and exposed to glucidic stress and streptozotocin-induced endothelial ADAM17 knockout mice. Evaluation of vascular permeability, vascular inflammation, and oxidative stress was performed. Loss of ADAM17 in endothelial cells markedly reduced oxidative stress evidenced by decreased levels of superoxide, 3-nitrotyrosine, and 4-hydroxynonenal and decreased leukocyte-endothelium adhesive interactions in vivo and in vitro. Reduced leukostasis was associated with decreased vascular permeability and was accompanied by downregulation of intercellular adhesion molecule-1 expression. Reduction in oxidative stress in HREC was associated with downregulation of NAD(P)H oxidase 4 (Nox4) expression. Our data suggest a role for endothelial ADAM17 in DR pathogenesis and identify ADAM17 as a potential new therapeutic target for DR.

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Section: Glucidic Stress Upregulates Expression Of Adam17 In Hrecsupporting

confidence: 94%

Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy

Shalaby

Thounaojam

Tawfik

et al. 2020

JCM

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“…ICAM-1 and its ligand CD18 play an important role in mediating leukocyte adhesion 27 , and inhibition of ICAM-1 results in significant mitigation of leukocyte adhesion and vasopermeability 28 . Expression of TNF-α is also upregulated in the retina under DR conditions 29 . The expression levels of both inflammatory factors in the retina of the GLUT1 siRNA group were only 66.14% and 54.76% of those in the diabetic scrambled siRNA group.…”

Section: Discussionmentioning

confidence: 96%

Suppression of diabetic retinopathy with GLUT1 siRNA

You

Zhang

Shi

et al. 2017

Sci Rep

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To investigate the effect of glucose transporter-1 (GLUT1) inhibition on diabetic retinopathy, we divided forty-eight mice into scrambled siRNA, diabetic scrambled siRNA, and GLUT1 siRNA (intravitreally injected) groups. Twenty-one weeks after diabetes induction, we calculated retinal glucose concentrations, used electroretinography (ERG) and histochemical methods to assess photoreceptor degeneration, and conducted immunoblotting, leukostasis and vascular leakage assays to estimate microangiopathy. The diabetic scrambled siRNA and GLUT1 siRNA exhibited higher glucose concentrations than scrambled siRNA, but GLUT1 siRNA group concentrations were only 50.05% of diabetic scrambled siRNA due to downregulated GLUT1 expression. The diabetic scrambled siRNA and GLUT1 siRNA had lower ERG amplitudes and ONL thicknesses than scrambled siRNA. However, compared with diabetic scrambled siRNA, GLUT1 siRNA group amplitudes and thicknesses were higher. Diabetic scrambled siRNA cones were more loosely arranged and had shorter outer segments than GLUT1 siRNA cones. ICAM-1 and TNF-α expression levels, adherent leukocyte numbers, fluorescence leakage areas and extravasated Evans blue in diabetic scrambled siRNA were higher than those in scrambled siRNA. However, these parameters in the GLUT1 siRNA were lower than diabetic scrambled siRNA. Together, these results demonstrate that GLUT1 siRNA restricted glucose transport by inhibiting GLUT1 expression, which decreased retinal glucose concentrations and ameliorated diabetic retinopathy.Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM). DR often results in decreased vision and even blindness caused by macular edema, retinal detachment, and vitreous hemorrhage. The number of patients with diabetes may grow to 642 million in 2040 1 . DR has been recognized as a microangiopathy, as well as a neurodegenerative disease. Although the detailed mechanism underlying DR is unclear, two major global multicenter studies on diabetes, DCCT 2 and UKPDS 3 , have revealed that a long-term high blood glucose level is the decisive factor for DR development. Moreover, excessive generation of retinal oxidative stress products 4 , activated protein kinase C 5 , and increased synthesis of glycosylated end products 6 under the environment of high blood glucose levels initiate the impairment of retinal tissues and cells 4 . Since lesions are induced by high blood glucose levels, we hypothesize that DR progression can be relieved by restricting glucose transfer into the retina, thereby decreasing its local glucose content. Glucose transporter-1 (GLUT1) is the only currently known carrier of glucose through the blood-retinal barrier and is also responsible for the distribution of glucose in ganglion cells, photoreceptor cells, and Müller cells in the retina; GLUT1 is primarily expressed in the vascular endothelial cells of the inner blood-retinal barrier and retinal pigment epithelial cells of the outer blood-retinal barrier 7 . GLUT1 was identified as a promising target...

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“…The IGFBP-3 gene in cattle is located on chromosome four, consist of 4 introns and 5 exons (Kim et al 2005), and the gene is approximately 8.407 bp length (GenBank; www.ncbi.nlm.nih.gov). Growth trait in mammals are affected by various hormones, one of them is Insulin-Like Growth Factor system (IGFs) (Zhang and Steinle 2014). IGFs hormone functions and capabilities are modulated by its binding protein, called Insulin-Like Growth Factor Binding Protein (IGFBP).…”

Section: Introductionmentioning

confidence: 99%

Short Communication: Population structure of mangrove crab Scylla oceanica in mangrove ecosystem of Tanjung Lesung, Banten, Indonesia

et al. 2017

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Abstract. Priyadi DA, Panjono, Bintara S, Hartatik T. 2017. The genotype of gene sequences. Biodiversitas 18: 795-800. The IGFBP-3 gene is a potential marker of cattle growth, which is related to the functions that influence the growth, energy metabolism, reproduction and immunity. The genome was isolated from whole blood samples of 10 Brahman cattle and 16 Brahman Cross cattle. Cattle IGFBP-3 gene that targeted in this study was located in the part of intron 2, exon 3 and part of intron 3. The gene targets were amplified using specific primers by Polymerase Chain Reaction (PCR) technique, resulting 563 bp amplification product. As data comparison to reveal the SNP, the GenBank sequences (n = 14) from various breed and countries were used. The objective of this study was to reveal the SNP on the Brahman and Brahman Cross IGFBP-3 gene. The results obtained 3 genotypes from one SNP that spread in the sample population. The SNP was located in intron 2 at position 3,930 (GA). The Polymorphism could be recognized by PvuII restriction enzymes. There was not enough evidence to associate the SNP with the phenotype (at pre-weaning age) of Brahman and Brahman Cross cattle. There was a genetic diversity in the population studied. Knowledgeable SNP could be used as genetic markers for further research on Brahman and Brahman Cross cattle.

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IGFBP-3 inhibits TNF-α production and TNFR-2 signaling to protect against Retinal Endothelial Cell Apoptosis

Cited by 29 publications

References 41 publications

Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy

Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy

Suppression of diabetic retinopathy with GLUT1 siRNA

Short Communication: Population structure of mangrove crab Scylla oceanica in mangrove ecosystem of Tanjung Lesung, Banten, Indonesia

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