Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke

Wang, Lu; Zhang, Xinyu; Liu, Xinghui; Feng, Gang; Fu, Yuan; Milner, Richard; Li, Longxuan

doi:10.1016/j.expneurol.2019.113042

Cited by 28 publications

(26 citation statements)

References 41 publications

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“…Besides indispensable roles in mammalian developmental cardiovascular formation and the maintenance of adult vascular stability, increasing evidence shows that after brain trauma, Angpt1 functions in a dual way in promoting angiogenesis and neurogenesis to enhance BBB integrity and neurological regeneration (Meng et al, 2014; Michinaga and Koyama, 2019; Wang et al, 2019). Moreover, in neural cell cultures, Angpt1 acts directly on neurite outgrowth via a beta1-integrin-dependent manner instead of binding to its typical receptor, Tek (Carlson et al, 2001; Chen et al, 2009a).…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development

Y¹,

Martins²,

Marchica³

et al. 2021

Preprint

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This study aimed at identifying the role of angiopoietin 1 (angpt1) in brain development, the mode of action of angpt1, and the main targets in the zebrafish brain. We investigated embryonic brain angiogenesis and neural development in the angpt1sa14264, itgb1bmi371, tekhu1667 mutant fish, and the effects of transgenic overexpression of angpt1 in the larval brain. Lack of angpt1 was associated with downregulation of tek and upregulation of itgb1b. We found deficiencies in the patterning of proliferation, the vascular network and reticulospinal neurons in the hindbrain, and selective deficiencies in specific neurotransmitter systems. In the angpt1sa14264 and itgb1bmi371 larval brains, using microangiography, retrograde labeling, and immunostaining, we demonstrated that the targeted destruction of angpt1sa14264 and itgb1bmi371 mutant fish caused severe irregular cerebrovascular development, aberrant hindbrain patterning, downregulation of neural proliferation, expansion of the radial glial progenitors, deficiencies of dopaminergic, histaminergic, and GABAergic populations in the larval brain. In contrast, the tekhu1667 mutants regularly grew with no such apparent phenotypes. Neurally overexpressed angpt1 promoted opposite effects by increasing the vascular branching, increasing cell proliferation, and neuronal progenitors. Notably, zebrafish angpt1 showed neurogenic activity independent of its typical receptor tek, indicating the novel role of a dual regulation by angpt1 in embryonic neurogenesis and angiogenesis in zebrafish. The results show that angpt1 and its interaction with itgb1b are crucial in zebrafish brain neuronal and vascular development and suggest that angpt1 through itgb1b can act as a neurogenic factor in the neural proliferation fate in the developing brain.

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Section: Discussionmentioning

confidence: 99%

Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development

Y¹,

Martins²,

Marchica³

et al. 2021

Preprint

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“…[ 60,115,116 ] Ang‐I's role in barrier stability was shown by Ang‐I positively regulating B‐catenin in BMECs, through activation of Akt and GSK2B phosphorylation, leading to the upregulation of Notch signaling. [ 116 ]…”

Section: Ang Signalingmentioning

confidence: 99%

Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models

Schofield

Rodrigo‐Navarro

Dalby

et al. 2021

Advanced NanoBiomed Research

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Central nervous system (CNS) pathologies are a prevalent problem in aging populations, creating a need to understand the underlying events in these diseases and develop efficient CNS‐targeting drugs. The importance of the blood–brain barrier (BBB) is evident, acting both as a physical barrier to drug entry into the CNS and potentially as the cause or aggravator of CNS diseases. The development of a biomimetic BBB in vitro model is required for the understanding of BBB‐related pathologies and in the screening of drugs targeting the CNS. There is currently great interest in understanding the influence of biochemical and biophysical factors, as these have the potential to greatly improve the barrier function of brain microvascular endothelial cells (BMECs). Recent advances in understanding how these may regulate barriergenesis in BMECs help promote the development of improved BBB in vitro models and therefore novel interventional therapies for pathologies related to its disruption. Herein, an overview of specific biochemical and biomechanical cues in the formation of the BBB, with a focus on in vitro models and how these might recapitulate the BBB function, is provided.

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“…Small interfering RNA (siRNA) and plasmid construction were performed as previously reported [22,23]. Briefly, three specific sequences of siRNA targeting the murine KLF4 (①sense 5′-GGUUUAUAUUGAAUCCAAAGA-3′, antisense 5′-UUUGGAUUCAAUAUAAACCGG-3′; ② sense 5′-GGUCAUCAGUGUUAGCAAAGG-3′, antisense 5′-UUUGCUAACACUGAUGACCGA-3′; and ③ sense 5′-GGAGAAAGGAAGAGUUCAAGA-3′, antisense 5′-UUG AACUCUUCCUUUCUCCUG-3′) were designed and synthesized by Gene Pharma (Shanghai, China).…”

Section: Construction and Transfection Of Sirna And Pcdna31 Plasmidsmentioning

confidence: 99%

KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke

Zhang

Wang

Zhengkang

et al. 2020

J Neuroinflammation

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Background: Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 have all been reported to be induced after cerebral ischemic stroke (CIS), the close temporal and spatial relationship between expressions of CAMs and KLF4 following CIS and whether and how CAMs and KLF-4 contribute to the development of CIS-induced vascular injury are still unclear. Methods: Here, we first examined the correlation between serum levels of CAMs/KLF4 and infarct volume in acute CIS patients. Then, we determined the relationship between CAMs and KLF4 in mice after focal cerebral ischemia. Finally, we investigated the mechanism of KLF4 in protecting against oxygen-glucose deprivation-induced brain endothelial cell injury.

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Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke

Cited by 28 publications

References 41 publications

Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development

Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development

Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models

KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke

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