Elevated expression levels of serum insulin‐like growth factor‐1, tumor necrosis factor‐α and vascular endothelial growth factor 165 might exacerbate type 2 diabetic nephropathy

Li, Xiang; Wu, Tingting; Chen, Juan; Qiu, Wen‐Ze

doi:10.1111/jdi.12542

Cited by 44 publications

(36 citation statements)

References 36 publications

(45 reference statements)

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“…In accordance with recent studies [8, 18-20], through measuring plasma levels of VEGF, IL-1β, IL-6, TNF-α, and TLR4 we found that inflammatory factors and VEGF expression were higher in patients with DPN than in DN patients. These findings are in agreement with the theory that DPN may be associated with inflammation and endothelial dysfunction [21].…”

Section: Discussionsupporting

confidence: 70%

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Tang

Chen

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. Methods: We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Results: Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Conclusions: Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury.

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Section: Discussionsupporting

confidence: 70%

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Tang

Chen

Liu

et al. 2018

Cell Physiol Biochem

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“…In addition, impaired PI3K-Akt signaling was reported in the myocardium of type 2 diabetic patients with chronic coronary heart disease, coupling with upregulated VEGFA 71 . Elevated VEGFA165 was also reported to exacerbate human type-2 diabetic nephropathy 77 , and administration of VEGFA neutralizing antibody resulted in amelioration of long-term renal changes in obese type-2 diabetic mice 78 . Thus, it will be interesting to know whether upregulated VEGFA associates with deficient phosphoinositide recycling in diabetic condition in heart or kidney, and tissue/organ specific signaling crosstalking and metabolic status must be considered to elucidate the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition

et al. 2019

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The response of endothelial cells to signaling stimulation is critical for vascular morphogenesis, homeostasis and function. Vascular endothelial growth factor-a (VEGFA) has been commonly recognized as a pro-angiogenic factor in vertebrate developmental, physiological and pathological conditions for decades. Here we report a novel finding that genetic ablation of CDP-diacylglycerol synthetase-2 (CDS2), a metabolic enzyme that controls phosphoinositide recycling, switches the output of VEGFA signaling from promoting angiogenesis to unexpectedly inducing vessel regression. Live imaging analysis uncovered the presence of reverse migration of the angiogenic endothelium in cds2 mutant zebrafish upon VEGFA stimulation, and endothelium regression also occurred in postnatal retina and implanted tumor models in mice. In tumor models, CDS2 deficiency enhanced the level of tumorsecreted VEGFA, which in-turn trapped tumors into a VEGFA-induced vessel regression situation, leading to suppression of tumor growth. Mechanistically, VEGFA stimulation reduced phosphatidylinositol (4,5)-bisphosphate (PIP2) availability in the absence of CDS2-controlled-phosphoinositide metabolism, subsequently causing phosphatidylinositol (3,4,5)-triphosphate (PIP3) deficiency and FOXO1 activation to trigger regression of CDS2-null endothelium. Thus, our data indicate that the effect of VEGFA on vasculature is context-dependent and can be converted from angiogenesis to vascular regression.

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“…Previous studies suggested that levels of TNF-α are increased in all DN patients irrespective of gender and therefore TNF-α can be considered as a biomarker of DN [17,18]. Furthermore, several case-control studies conducted by Li et al and Babel et al [19,20] reported that elevated expression levels of serum TNF-α might exacerbate type 2 DN. Some studies have investigated the association between the TNF-α-308G/A polymorphism (rs1800629) and diabetic retinopathy in different populations [21,22].…”

Section: Introductionmentioning

confidence: 99%

Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis

et al. 2020

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Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03–1.83) and homozygous model (OR=1.54, 95% CI=1.15–2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18–2.42; homozygous: OR=1.99, 95% CI=1.38–2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02–1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.

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Elevated expression levels of serum insulin‐like growth factor‐1, tumor necrosis factor‐α and vascular endothelial growth factor 165 might exacerbate type 2 diabetic nephropathy

Cited by 44 publications

References 36 publications

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition

Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis

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