Phosphorylation of Dab2 is involved in inhibited VEGF‐VEGFR‐2 signaling induced by downregulation of syndecan‐1 in glomerular endothelial cell

Zhou, Jian; Wang, Yuan

doi:10.1002/cbin.11288

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…The release of syndecan-1 from damaged nerve cells is thought to activate immune cells and promote tissue repair [7]. In addition, studies in the literature show that it increases neurogenesis in nerve tissue after injury [8].…”

Section: Of 13mentioning

confidence: 99%

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model

Yalçın,

Bora,

Erdoğan

et al. 2023

JCM

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Peripheral nerve damage is a significant clinical problem with limited therapeutic options. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic approach due to their regenerative potential. However, the underlying mechanisms by which ADSCs promote peripheral nerve regeneration remain unclear. In this study, we investigated the role of syndecan-1 and heat shock protein 70 (HSP-70) in mediating the regenerative effects of ADSCs on peripheral nerves. ADSCs were characterized and isolated from the adipose tissue of rats. In vitro experiments were conducted to evaluate the ability of ADSCs to secrete syndecan-1 and HSP-70 in response to stress conditions. To evaluate the therapeutic potential of ADSCs, rats with sciatic nerve injuries were treated with ADSCs and assessed for functional recovery, nerve regeneration, and changes in syndecan-1 and HSP-70 levels. Regeneration was evaluated with Electromyography (EMG) histology. The results showed that ADSCs could secrete syndecan-1 and HSP-70 in response to stress conditions. Furthermore, ADSC treatment significantly improved functional recovery and nerve regeneration and increased syndecan-1 and HSP-70 levels in the injured nerve. On the other hand, ADSCs make improvements histologically through the influence of Nerve growth factor (NGF), Malondialdehyde (MDA), and EMG.

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Section: Of 13mentioning

confidence: 99%

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model

Yalçın,

Bora,

Erdoğan

et al. 2023

JCM

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Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing

Bhattacharjee,

Gao,

et al. 2024

Preprint

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This study investigates the molecular underpinnings of endothelial dysfunction in diabetes, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGFR2 signaling and endothelial cell function. Our research reveals critical insights into the downregulation of Dab2 and FoxM1 in endothelial cells (ECs) under hyperglycemic conditions that leads to impaired angiogenesis and delayed wound healing. These findings Substantiate our hypothesis that restoring Dab2 expression through targeted therapies could enhance angiogenesis and wound repair in diabetic environments. In vitro experiments involved treating primary murine brain ECs with high glucose concentrations, simulating hyperglycemic conditions in diabetes mellitus. Bulk RNA-sequencing analysis identified significant downregulation of Dab2, FoxM1, and genes involved in cell cycle progression, cell growth, survival, glycolysis, and oxidative phosphorylation. In vivo, ECs isolated from diabetic mice showed a marked decrease in Dab2 and FoxM1 compared to controls, validated by immunostaining and western blot analysis. Notably, FoxM1 was found to directly bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. Dab2 deficiency led to enhanced lysosomal degradation of VEGFR2 in high-glucose-treated ECs, reducing VEGFR2 signaling. This was further supported by in vitro experiments showing decreased proliferation and angiogenic capability in Dab2-deficient brain ECs. Correspondingly, diabetic mice lacking Dab2 exhibited slower wound healing and reduced neovascularization. To explore therapeutic potential, we employed Dab2-mRNA encapsulated in lipid nanoparticles, significantly improving wound healing and angiogenesis in diabetic mice. This study provides substantial evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and proposes targeted gene delivery systems as a promising treatment for diabetic vascular complications.

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Disabled-2 (DAB2): A Key Regulator of Anti- and Pro-Tumorigenic Pathways

Price

Lokman

Yoshihara

et al. 2022

IJMS

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Disabled-2 (DAB2), a key adaptor protein in clathrin mediated endocytosis, is implicated in the regulation of key signalling pathways involved in homeostasis, cell positioning and epithelial to mesenchymal transition (EMT). It was initially identified as a tumour suppressor implicated in the initiation of ovarian cancer, but was subsequently linked to many other cancer types. DAB2 contains key functional domains which allow it to negatively regulate key signalling pathways including the mitogen activated protein kinase (MAPK), wingless/integrated (Wnt) and transforming growth factor beta (TGFβ) pathways. Loss of DAB2 is primarily associated with activation of these pathways and tumour progression, however this review also explores studies which demonstrate the complex nature of DAB2 function with pro-tumorigenic effects. A recent strong interest in microRNAs (miRNA) in cancer has identified DAB2 as a common target. This has reignited an interest in DAB2 research in cancer. Transcriptomics of tumour associated macrophages (TAMs) has also identified a pro-metastatic role of DAB2 in the tumour microenvironment. This review will cover the broad depth literature on the tumour suppressor role of DAB2, highlighting its complex relationships with different pathways. Furthermore, it will explore recent findings which suggest DAB2 has a more complex role in cancer than initially thought.

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Phosphorylation of Dab2 is involved in inhibited VEGF‐VEGFR‐2 signaling induced by downregulation of syndecan‐1 in glomerular endothelial cell

Cited by 3 publications

References 34 publications

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing

Disabled-2 (DAB2): A Key Regulator of Anti- and Pro-Tumorigenic Pathways

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