Spatio-temporal expression pattern and role of the tight junction protein MarvelD3 in pancreas development and function

AbstractTight junction complexes are involved in the establishment and maintenance of cell polarity and the regulation of signalling pathways, controlling biological processes such as cell differentiation and cell proliferation. MarvelD3 is a tight junction protein expressed in adult epithelial and endothelial cells. In Xenopus laevis, MarvelD3 morphants present differentiation defects of several ectodermal derivatives. In vitro experiments further revealed that MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behaviour and survival. In this work, we found that MarvelD3 is expressed from early developmental stages in the exocrine and endocrine compartments of the pancreas, as well as in endothelial cells of this organ. We thoroughly characterized MarvelD3 expression pattern in developing pancreas and evaluated its function by genetic ablation. Surprisingly, inactivation of MarvelD3 in mice did not alter development and differentiation of the pancreatic tissue. Moreover, tight junction formation and organization, cell polarization, and activity of the JNK-pathway were not impacted by the deletion of MarvelD3.

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Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly

Cell Death Discovery ◽

10.1038/s41420-021-00548-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yi-Fang Tu ◽

Si-Tse Jiang ◽

Chi-Wu Chiang ◽

Li-Ching Chen ◽

Chao-Ching Huang

Keyword(s):

Endothelial Cells ◽

Brain Injury ◽

Tight Junction ◽

Insulin Receptor ◽

Vascular Endothelial Cells ◽

Tight Junction Protein ◽

Insulin Receptor Substrate ◽

Vascular Endothelial ◽

Transgenic Rats ◽

Junction Protein

AbstractHypoxic-ischemic (HI) encephalopathy is the major cause of mortality and disability in newborns. The neurovascular unit is a major target of acute and chronic brain injury, and therapies that protect simultaneously both neurons and vascular endothelial cells from neonatal HI injury are in demand. Insulin receptors and its key downstream molecule-insulin receptor substrate −1 (IRS-1) are potential neuroprotective targets and expressed both in neuron and endothelial cells. To investigate whether IRS-1 can act similarly in neurons and vascular endothelial cells in protecting neurovascular units and brain form HI injury, we found that neuron-specific IRS-1 transgenic rats showed reduced neurovascular injury and infarct volumes, whereas endothelial-specific IRS-1 transgenic rats showed increased blood-brain barrier (BBB) disruption and exaggerated neurovascular injury after neonatal HI brain injury. Endothelial-specific IRS-1 overexpression increased vascular permeability and disassembled the tight junction protein (zonula occludens-1) complex. Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Together, our findings suggested that neuronal and endothelial IRS-1 had opposite effects on the neurovascular integrity and damage after neonatal HI brain injury and that endothelial IRS-1 worsens neurovascular integrity after HI via mTOR-mediated tight junction protein disassembly.

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Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells

Brain Research ◽

10.1016/j.brainres.2006.10.083 ◽

2007 ◽

Vol 1130 ◽

pp. 17-30 ◽

Cited By ~ 188

Author(s):

Rachel C. Brown ◽

Andrew P. Morris ◽

Roger G. O'Neil

Keyword(s):

Endothelial Cells ◽

Protein Expression ◽

Tight Junction ◽

Mouse Brain ◽

Barrier Properties ◽

Tight Junction Protein ◽

Tight Junction Protein Expression ◽

Junction Protein ◽

Microvessel Endothelial Cells ◽

Brain Microvessel

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Effects of fasudil on blood-brain barrier integrity

10.21203/rs.3.rs-1116440/v1 ◽

2021 ◽

Author(s):

Kei Sato ◽

Shinsuke Nakagawa ◽

Yoichi Morofuji ◽

Yuki Matsunaga ◽

Takashi Fujimoto ◽

...

Keyword(s):

Endothelial Cells ◽

Ischemic Stroke ◽

Tight Junction ◽

Acute Ischemic Stroke ◽

Blood Brain Barrier ◽

Tight Junction Protein ◽

Brain Barrier ◽

Blood Brain ◽

Junction Protein ◽

Culture Models

Abstract Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Medhods: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6-hour OGD/24-hour reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using immunohistochemistry and western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3–30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.

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Rho signaling is involved in HIV‐1 Tat‐induced tight junction protein ZO‐1 translocation and alterations of claudin‐5 expression in brain endothelial cells

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.867.6 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Yu Zhong ◽

Bernhard Hennig ◽

Michal Toborek

Keyword(s):

Endothelial Cells ◽

Tight Junction ◽

Tight Junction Protein ◽

Brain Endothelial Cells ◽

Junction Protein ◽

Hiv 1

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Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system

European Journal of Pharmacology ◽

10.1016/j.ejphar.2019.04.021 ◽

2019 ◽

Vol 854 ◽

pp. 224-231 ◽

Cited By ~ 9

Author(s):

Changxiang Li ◽

Xueqian Wang ◽

Fafeng Cheng ◽

Xin Du ◽

Juntang Yan ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Tight Junction ◽

Blood Brain Barrier ◽

Tight Junction Protein ◽

Brain Barrier ◽

In Vitro System ◽

Tight Junction Protein Expression ◽

Junction Protein

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Layilin is critical for mediating hyaluronan 35 kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo

Matrix Biology ◽

10.1016/j.matbio.2017.09.003 ◽

2018 ◽

Vol 66 ◽

pp. 93-109 ◽

Cited By ~ 12

Author(s):

Yeojung Kim ◽

Gail A. West ◽

Greeshma Ray ◽

Sean P. Kessler ◽

Aaron C. Petrey ◽

...

Keyword(s):

Tight Junction ◽

Tight Junction Protein ◽

Intestinal Epithelial ◽

Junction Protein ◽

Epithelial Tight Junction

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RETRACTED: Gene expression pattern analysis of the tight junction protein, Claudin, in the early morphogenesis of Xenopus embryos

Gene Expression Patterns ◽

10.1016/s0925-4773(02)00348-9 ◽

2002 ◽

Vol 2 (1-2) ◽

pp. 23-26 ◽

Cited By ~ 4

Author(s):

Makiko Fujita ◽

Mari Itoh ◽

Mikihito Shibata ◽

Sumiko Taira ◽

Masanori Taira

Keyword(s):

Gene Expression ◽

Tight Junction ◽

Expression Pattern ◽

Pattern Analysis ◽

Gene Expression Pattern ◽

Tight Junction Protein ◽

Xenopus Embryos ◽

Expression Pattern Analysis ◽

Junction Protein

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Tight junction protein claudin-6 inhibits growth and induces the apoptosis of cervical carcinoma cells in vitro and in vivo

Medical Oncology ◽

10.1007/s12032-015-0600-4 ◽

2015 ◽

Vol 32 (5) ◽

Cited By ~ 14

Author(s):

Xiaowei Zhang ◽

Yang Ruan ◽

Yanru Li ◽

Dongjing Lin ◽

Chengshi Quan

Keyword(s):

Tight Junction ◽

Cervical Carcinoma ◽

Carcinoma Cells ◽

Tight Junction Protein ◽

Junction Protein

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AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells

Molecular Biology of the Cell ◽

10.1091/mbc.e19-03-0179 ◽

2020 ◽

Vol 31 (2) ◽

pp. 118-130 ◽

Cited By ~ 3

Author(s):

Patrizia Brunner ◽

Nurcan Hastar ◽

Christian Kaehler ◽

Wiktor Burdzinski ◽

Jerome Jatzlau ◽

...

Keyword(s):

Endothelial Cells ◽

Tight Junction ◽

Apical Membrane ◽

Tight Junction Protein ◽

Smad Signaling ◽

Bmp Receptor ◽

Apical Side ◽

Junction Protein ◽

Polarized Cells

We found that the tight-junction protein angiomotin (AMOT130) interacts with the BMP receptor BMPR2 and thereby supports BMP/SMAD signaling exclusively at the apical side of polarized epithelial and endothelial cells. BMP-mediated internalization of AMOT discerns BMPs as novel regulators of AMOT function.

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