Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria

He, Fang-Fang; Li, Huiqing; Huang, Qing; Wang, Qiuyuan; Jiang, Haiyue; Chen, Shan; Su, Hua; Zhang, Chun; Wang, Yumei

doi:10.1159/000368510

Cited by 12 publications

(9 citation statements)

References 37 publications

(41 reference statements)

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“…In type 2 diabetic patients, serum and urine TNF-α level increased significantly with the degree of albuminuria [15]. In rats with renal failure, TNF-α naturalization prevented albuminuria, reduced fibrosis, decreased macrophage infiltration [16, 17].…”

Section: Introductionmentioning

confidence: 99%

TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice

Wang¹,

Gai

et al. 2017

Kidney Blood Press Res

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Background/Aims: Obese patients and experimental animals exhibit high levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α. However, the role of TNF-α in the pathophysiologic process in obesity induced kidney damage is still unknown. Methods: We used TNF-α deficient mice and wild-type (WT) C57/BJ6 mice controls to study the effect of TNF-α on inflammation and oxidative stress in kidney by the model of high-fat diet (HFD) and primary isolated mouse renal proximal tubule cells treated with a mixture of free fatty acids (FFA). Results: Compared with the chow diet group, HFD-fed WT mice had higher urinary albumin and increased levels of renal fibrosis, glomerulosclerosis, inflammation, oxidative stress and apoptosis in the kidney. These changes were co-related with increased expression of TNF-α in the kidney and were attenuated by TNF-α deficiency. In vitro, accumulation of intracellular lipids induced TNF-α expression and oxidative stress in FFA treated primary proximal tubule cells. However, TNF-α inhibition with siRNA or TNF-α deficiency decreased the lipid induced oxidative stress in these cells. Conclusion: These findings suggest that TNF-α plays an important role in the HFD induced kidney damage, and targeting TNF-α and/or its receptors could be a promising therapeutic regimen for progressive nephropathy.

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Section: Introductionmentioning

confidence: 99%

TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice

Wang¹,

Gai

et al. 2017

Kidney Blood Press Res

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“…Ang2 overexpression-induced albuminuria and glomerular endothelial apoptosis were found to be consistent with the upregulation of VEGF-A signaling and nephrin phosphorylation in diabetic disease [44,[57][58][59]. A recent study demonstrated that upregulation of Ang2 in the urinary was associated with TNF-a and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG, a type of reactive oxygen species) in type 2 diabetic patients with albuminuria, but the mechanism was unclear [61]. A recent study demonstrated that upregulation of Ang2 in the urinary was associated with TNF-a and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG, a type of reactive oxygen species) in type 2 diabetic patients with albuminuria, but the mechanism was unclear [61].…”

Section: Diabetic Nephropathymentioning

confidence: 87%

Angiopoietin‐Tie signaling in kidney diseases: an updated review

Zhang

Chen

et al. 2019

FEBS Letters

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Angiopoietins (Angs) are a family of vascular growth factors that share multiple cellular functions related to cell survival, proliferation, and migration. Angs play physiological and pathological roles through the Tie tyrosine kinase receptors. The Ang‐Tie signaling pathway participates in the developmental and tumor‐induced angiogenesis and is also involved in many disease settings, such as vascular diseases, systemic inflammation, and cancers. Since Angs are widely expressed in the kidney, an enormous amount of research focuses on their roles in the kidney. In this review, we describe the biological functions of the Ang‐Tie signaling pathway and summarize their roles in kidney development and maturation, acute and chronic kidney diseases, diabetic nephropathy, lupus nephropathy, hemolytic uremic syndrome, end‐stage renal diseases, and renal cell carcinoma. Understanding the molecular mechanisms of Ang‐Tie signaling may reveal potential therapeutic targets for preventing or alleviating kidney diseases.

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“…Increased levels of Ang2 are associated with worsening of renal structure, and Ang2 is elevated in the serum and urine of diabetic patients [76,77]. Furthermore, TNFα and ROS are associated with elevated urinary Ang2 levels in albuminuric T2DM patients [78]. Glomerular lesions, mesangial expansion, podocyte lesions and a disturbed Ang2/Ang1 balance in the cortex of the kidney were found in a pig model of diabetes [79].…”

Section: Diabetic Nephropathymentioning

confidence: 98%

Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes

Isidori

Venneri

Fiore

2016

J Endocrinol Invest

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The morbidity and mortality of diabetes mellitus are mostly attributed to cardiovascular complications. Despite tremendous advancement in glycemic control, anti-diabetic medications have failed to revert vascular impairment once triggered by the metabolic disorder. The angiogenic growth factors, Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2), are crucial regulators of vessel formation and maintenance starting with embryonic development and continuing through life. In mature vessels, angiopoietins control vascular permeability, inflammation and remodeling. A crucial role of angiopoietins is to drive vascular inflammation from the active to the quiescent state, enabling restoration of tissue homeostasis. The mechanism is of particular importance for healing and repair after damage, two conditions typically impaired in metabolic disorders. There is an emerging body of evidences suggesting that the imbalance of Ang1 and Ang2 regulation, leading to an increased Ang2/Ang1 ratio, represents a culprit of the vascular alterations of patients with type-2 diabetes mellitus. Pharmacological modulation of Ang1 or Ang2 actions may help prevent or delay the onset of diabetic vascular complications by restoring vessel function, favoring tissue repair and maintaining endothelial quiescence. In this review, we present a summary of the role of Ang1 and Ang2, their involvement in diabetic complications, and novel therapeutic strategies targeting angiopoietins to ameliorate vascular health in metabolic disorders.

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Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria

Cited by 12 publications

References 37 publications

TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice

TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice

Angiopoietin‐Tie signaling in kidney diseases: an updated review

Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes

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