Baicalin Protects against TNF-α-Induced Injury by Down-Regulating miR-191a That Targets the Tight Junction Protein ZO-1 in IEC-6 Cells

Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

Download Full-text

Spermine Protects Intestinal Barrier Integrity Through Rac1/PLC-γ1 Signalling Pathway in Piglets

10.21203/rs.3.rs-102466/v1 ◽

2020 ◽

Author(s):

Guangmang Liu ◽

Xiaomei Xu ◽

Caimei Wu ◽

Gang Jia ◽

Hua Zhao ◽

...

Keyword(s):

Tight Junction ◽

Intestinal Barrier ◽

Signalling Pathway ◽

Tight Junction Protein ◽

Intestinal Integrity ◽

Tnf Α ◽

Junction Protein ◽

Intestinal Barrier Integrity

Abstract Background: Weaning stress can lead to the disruption of tight junctions and increased intestinal permeabilty, which contributes to the initiation and development of many disease, such as Crohn’s disease and ulcerative colitis. Pigs are more ideal models for human studies than other animals. However, no information is found about the relationship of intestinal integrity and spermine supplementation in pigs. The objective of this study is to investigate whether spermine protects intestinal barrier integrity via Rac1/PLC-γ1 signalling pathway in piglets. Methods: In vivo, the piglets were categorised into the control group and the spermine group, which was fed with spermine at 0.4 mmol kg−1 body weight for 7 hours and 3, 6 and 9 days. In vitro, we examined whether spermine protects the intestinal barrier after TNF-α challenge through Ras-related C3 botulinum toxin substrate 1 (Rac1)/Phospho-lipase C-γ1 (PLC-γ1) signalling pathway. Results: In vivo study revealed that the spermine treatment upregulated tight junction protein mRNA levels and Rac1/PLC-γ1 signalling pathway gene expression in the jejunum of piglets. The serum D-lactate content was significantly reduced after spermine treatment (P < 0.05). In vitro study revealed that 0.1 μM spermine significantly increased the levels of tight junction protein expression, Rac1/PLC-γ1 signalling pathway and transepithelial electrical resistance, and decreased paracellular permeability (P < 0.05). Further experiments showed that spermine treatment increased the levels of tight junction protein expression, Rac1/PLC-γ1 signalling pathway and transepithelial electrical resistance, and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-α challenge (P < 0.05). Conclusion: spermine protects intestinal integrity through the Rac1/PLC-γ1 signalling pathway.

Download Full-text

Tight Junction Protein ZO-1 Staining Method

10.32388/dhoteb ◽

2020 ◽

Author(s):

Keyword(s):

Tight Junction ◽

Staining Method ◽

Tight Junction Protein ◽

Junction Protein

Download Full-text

Endothelial Tpl2 Regulates Vascular Barrier Function Via Tight Junction Protein Claudin-5 Promoting CNS Cell Infiltration and Tumor Metastasis

SSRN Electronic Journal ◽

10.2139/ssrn.3426154 ◽

2019 ◽

Author(s):

Aikaterini Nanou ◽

Stefania Vetrano ◽

Ute Schaeper ◽

Steven Ley ◽

George Kollias

Keyword(s):

Tight Junction ◽

Barrier Function ◽

Tumor Metastasis ◽

Tight Junction Protein ◽

Cell Infiltration ◽

Junction Protein

Download Full-text

Polycystin-2 Activity Is Controlled by Transcriptional Coactivator with PDZ Binding Motif and PALS1-associated Tight Junction Protein

Journal of Biological Chemistry ◽

10.1074/jbc.c110.146381 ◽

2010 ◽

Vol 285 (44) ◽

pp. 33584-33588 ◽

Cited By ~ 12

Author(s):

Kerstin Duning ◽

Deike Rosenbusch ◽

Marc A. Schlüter ◽

Yuemin Tian ◽

Karl Kunzelmann ◽

...

Keyword(s):

Tight Junction ◽

Tight Junction Protein ◽

Binding Motif ◽

Transcriptional Coactivator ◽

Junction Protein

Download Full-text

Exogenous GDF9 but not Activin A, BMP15 or TGFβ alters tight junction protein transcript abundance in zebrafish ovarian follicles

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2011.01.009 ◽

2011 ◽

Vol 171 (2) ◽

pp. 211-217 ◽

Cited By ~ 16

Author(s):

Eric S. Clelland ◽

Scott P. Kelly

Keyword(s):

Tight Junction ◽

Transcript Abundance ◽

Ovarian Follicles ◽

Activin A ◽

Tight Junction Protein ◽

Junction Protein

Download Full-text

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.

Download Full-text