Dll4-Notch1 signaling but not VEGF-A is essential for hyperoxia induced vessel regression in retina

Zhu, Guofu; Lin, Ying; Liu, Hao; Jiang, Da-Quan; Singh, Shekhar; Li, Xiankai; Yu, Ze; Fan, Linlin; Wang, Shumin; Rhen, Jordan; Li, Weiming; Xu, Yawei; Ge, Junbo; Pang, Jinjiang

doi:10.1016/j.bbrc.2018.11.051

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Therefore, there is a serious require for finding, and developing new effect therapeutic platforms combining anti-angiogenic therapies along with conventional cytoreductive treatments in the management of different cancers [83]. Vascular endothelial growth factor (VEGF) is significantly over-expresses in cancer patients [85, 86] VEGF inhibits apoptosis, protects tumor and vascular growth, and enhances proliferation and inflammation leading to carcinogenesis [87]. Melatonin decreases VEGF secretion resulting in inhibition of angiogenesis in tumors [88].…”

Section: Melatonin and Its Ani-angigenesis Effectsmentioning

confidence: 99%

Melatonin is a potential inhibitor of ovarian cancer: molecular aspects

et al. 2019

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Ovarian cancer is one of the most common causes of morbidity related to gynecologic malignancies. Possible risk factors are including hereditary ovarian cancer, obesity, diabetes mellitus, alcohol consumption, aging, and smoking. Various molecular signaling pathways including inflammation, oxidative stress, apoptosis and angiogenesis are involved in this progression of ovarian cancer. Standard treatments for recently diagnosed patients are Surgery and chemotherapy such as co-treatment with other drugs such that the exploitation of neoadjuvant chemotherapy is expanding. Melatonin (N-acetyl-5-methoxy-tryptamine), an endogenous agent secreted from the pineal gland, has anti-carcinogenic features, such as regulation of estradiol production, cell cycle modulation, stimulation of apoptosis as well as anti-angiogenetic properties, anti-inflammatory activities, significant antioxidant effects and modulation of various immune system cells and cytokines. Multiple studies have shown the significant beneficial roles of melatonin in various types of cancers including ovarian cancer. This paper aims to shed light on the roles of melatonin in ovarian cancer treatment from the standpoint of the molecular aspects.

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Section: Melatonin and Its Ani-angigenesis Effectsmentioning

confidence: 99%

Melatonin is a potential inhibitor of ovarian cancer: molecular aspects

et al. 2019

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“…To confirm the role of TAT‐ANK on Dll4‐Notch1 signalling, we measured Dll4 and cleaved Notch1 (NICD Val1744, activated Notch1) by immunofluorescent staining or signalling amplify system, as we have already published (Zhu et al, 2018). In the TAT‐Sc‐injected group, Dll4 was expressed in tip cells and arteries (Figure 6a), consistent with the others and our previous reports (Benedito et al, 2012; Majumder et al, 2014; Pitulescu et al, 2017; Zhu et al, 2018). NICD mainly localized in arteries and angiogenic plexus but not in veins (Figure 6b).…”

Section: Resultsmentioning

confidence: 99%

“…Retinal whole‐mount staining was carried out as described earlier (Majumder et al, 2016; Zhu et al, 2018). Briefly, eyes were fixed for 2 h at 4°C immersed in 4% PFA in PBS.…”

Section: Methodsmentioning

confidence: 99%

A novel peptide inhibitor of Dll4‐Notch1 signalling and its pro‐angiogenic functions

Zhu

Lin

et al. 2022

British J Pharmacology

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Background and Purpose: The Dll4-Notch1 signalling pathway plays an important role in sprouting angiogenesis, vascular remodelling and arterial or venous specificity.Genetic or pharmacological inhibition of Dll4-Notch1 signalling leads to excessive sprouting angiogenesis. However, transcriptional inhibitors of Dll4-Notch1 signalling have not been described.Experimental Approach: We designed a new peptide targeting Notch signalling, referred to as TAT-ANK, and assessed its effects on angiogenesis. In vitro, tube formation and fibrin gel bead assay were carried out, using human umbilical vein endothelial cells (HUVECs). In vivo, Matrigel plug angiogenesis assay, a developmental retinal model and tumour models in mice were used. The mechanisms underlying TAT-ANK activity were investigated by immunochemistry, western blotting, immunoprecipitation, RT-qPCR and luciferase reporter assays.

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“…Another important family of proteins downstream of Notch is the Hes family, of which Hes1, Hes2, Hes5 play an important role in regulating the proliferation, differentiation and neurogenesis of stem cells and vascular smooth muscle. Simultaneously, they have a synergistic effect with the angiogenesis effect of VEGF [31,32] . Studies have also reported the possible mechanism of Notch1 and VEGFA on the activation and transformation of astrocytes into neurons [33] .…”

Section: Discussionmentioning

confidence: 99%

Based on Dll4/Notch1 Signaling Pathway to Elucidate the Therapeutic Effect and Mechanism of L-borneolum on Cerebral Ischemic Stroke Rats

Dong¹,

Chen²,

Ma³

et al. 2021

Preprint

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Background: The current research progress suggests that a single therapy may not be ideal means for complex cerebral ischemic stoke (CIS). l-Borneolum is the crystallization of fresh leaves of Blumea balsamifera (L.) DC, we have found that l-borneolum plays a best anti-cerebral ischemic effect than d-borneolum or synthetic borneolum. However, the mechanism is needed to be explored in depth. Therefore, based on comprehensive approach that combines molecular docking technology and molecular biology, this stiudy aimed to investigate the potential mechanism of l-borneolum on CIS rats and provide scientific evidence for the treatment of l-borneolum in CIS.Methods: Cerebral ischemic stroke (CIS) rats with permanent middle cerebral artery occlusion (pMCAO) were applied to this study. The modified neurological severity scores (mNSS) and Longa neurological function scoring methods were used to assess the neurobehavioral scores. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to evaluate pathological changes of cerebral tissue. Ultrastructure of cortical capillary and blood-brain barrier (BBB) in rats were observed by transmission electron microscopy. In addition, the protein expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex of rats were determined by Western blotting (WB). The protein contents of Caspase 3 in the cortex of rats were determined by immunohistochemical method (IHC). Results: l-Borneolum could prolong the resuscitation time, reduce the abnormal increased rectal temperature, improve neurological function in a dose-dependently. Additionally, l-borneolum could significantly alleviate brainstem edema and inflammation, as well as improve the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum could substantially decrease the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while it decreased the level of Caspase-3 in the cortex of rats. Conclusions: l-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway, l-borneolum might be a good complementary agent for CIS.

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Dll4-Notch1 signaling but not VEGF-A is essential for hyperoxia induced vessel regression in retina

Cited by 7 publications

References 31 publications

Melatonin is a potential inhibitor of ovarian cancer: molecular aspects

Melatonin is a potential inhibitor of ovarian cancer: molecular aspects

A novel peptide inhibitor of Dll4‐Notch1 signalling and its pro‐angiogenic functions

Based on Dll4/Notch1 Signaling Pathway to Elucidate the Therapeutic Effect and Mechanism of L-borneolum on Cerebral Ischemic Stroke Rats

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