Targeting VE-PTP phosphatase protects the kidney from diabetic injury

Carota, Isabel Anna; Kenig-Kozlovsky, Yael; Onay, Tuncer; Scott, Rizaldy P.; Thomson, Benjamin R.; Souma, Tomokazu; Bartlett, Christina S.; Li, Yanyang; Procissi, Daniele; Ramirez, Veronica; Yamaguchi, Shinjiro; Tarjus, Antoine; Tanna, Christine E.; Li, Chengjin; Eremina, Vera; Vestweber, Dietmar; Oladipupo, Sunday S.; Breyer, Matthew D.; Quaggin, Susan E.

doi:10.1084/jem.20180009

Cited by 37 publications

(49 citation statements)

References 81 publications

(99 reference statements)

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“…Podocyte-specific overexpression of Ang1 gene reduced albuminuria and increased endothelial nitric oxide synthase [80]. Moreover, genetic deletion of VE-PTP that restored TIE2 activation protected renal structure and function in a murine model of diabetic nephropathy [82].…”

Section: Ang-tie Pathway In Alzheimer's Diseasementioning

confidence: 94%

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Hayashi

Rakugi

Morishita

2020

Cells

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Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected to permit clinical applications, especially in antiangiogenic therapies against tumors. Several drugs targeting the Ang-TIE signaling pathway in cancer patients are under clinical development. Similar to how cancer increases with age, unsuitable angiogenesis or endothelial dysfunction is often seen in other ageing-associated diseases (AADs) such as atherosclerosis, Alzheimer’s disease, type 2 diabetes, chronic kidney disease and cardiovascular diseases. Thus, the Ang-TIE pathway is a possible molecular target for AAD therapy. In this review, we focus on the potential role of the Ang-TIE signaling pathway in AADs, especially non-cancer-related AADs. We also suggest translational insights and future clinical applications of this pathway in those AADs.

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Section: Ang-tie Pathway In Alzheimer's Diseasementioning

confidence: 94%

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Hayashi

Rakugi

Morishita

2020

Cells

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“…Recent study revealed that the Tie2 signaling is attenuated by upregulated vascular endothelial protein tyrosine phosphatase in diabetic kidney in mice. While the activation of Tie2 protects the diabetic mice from the development of proteinuria, loss of GFR, and glomerular histopathological changes, this may be due to the activation that initiates the signaling events of PI3K and AKT, which increases eNOS phosphorylation and local NO production ( Carota et al, 2019 ). Consistently, the reduced Ang1/Tie2 signaling leads to increased unstable glomerular capillaries in hyaluronan synthase 2 knockout mouse model ( van den Berg et al, 2019 ; Wang et al, 2020 ).…”

Section: Other Angiogenic Factors Associated With Dnmentioning

confidence: 99%

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

et al. 2020

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Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.

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“…In certain circumstances, such as lymphangiogenesis [28], tumor models [29], pathogen-free conditions, or when Ang1 is absent [27,30], Ang2 functions as an agonist of Tie2 signaling and promotes Tie2 phosphorylation [31]. A new drug targeted to VE-PTP induced a reduction in proteinuria which may protect the kidney from diabetic injury [32]. VE-PTP is upregulated in diabetic animals and inhibition of VE-PTP activates endothelial nitric oxide synthase and decreased FOXO1 and its downstream profibrotic and pro-inflammatory targets.…”

Section: Ang Receptorsmentioning

confidence: 99%

“…VE-PTP is upregulated in diabetic animals and inhibition of VE-PTP activates endothelial nitric oxide synthase and decreased FOXO1 and its downstream profibrotic and pro-inflammatory targets. A new drug targeted to VE-PTP induced a reduction in proteinuria which may protect the kidney from diabetic injury [32].…”

Section: Ang Receptorsmentioning

confidence: 99%

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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Targeting VE-PTP phosphatase protects the kidney from diabetic injury

Cited by 37 publications

References 81 publications

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

Angiopoietin‐Tie signaling in kidney diseases: an updated review

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