scholarly journals Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins

2022 ◽  
pp. 105282
Author(s):  
Saori Nonaka ◽  
Tomoko Kadowaki ◽  
Hiroshi Nakanishi
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Porphyromonas Gingivalis ◽  
Microvascular Endothelial Cells ◽  
Tight Junction Proteins ◽  
Intracellular Degradation ◽  
Microvascular Endothelial ◽  
Junction Proteins

scholarly journals Colquhounia Root Tablet Protects Rat Pulmonary Microvascular Endothelial Cells against TNF-α-Induced Injury by Upregulating the Expression of Tight Junction Proteins Claudin-5 and ZO-1

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Wenjie Zhou ◽  
Guocui Shi ◽  
Jijia Bai ◽  
Shenmao Ma ◽  
Qinfu Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Microvascular Endothelial Cells ◽  
Protective Effects ◽  
Tight Junction Proteins ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Junction Proteins

Background. There are currently limited effective pharmacotherapy agents for acute lung injury (ALI). Inflammatory response in the lungs is the main pathophysiological process of ALI. Our preliminary data have shown that colquhounia root tablet (CRT), a natural herbal medicine, alleviates the pulmonary inflammatory responses and edema in a rat model with oleic acid-induced ALI. However, the potential molecular action mechanisms underlining its protective effects against ALI are poorly understood. This study aimed to investigate the effects and mechanism of CRT in rat pulmonary microvascular endothelial cells (PMEC) with TNF-α-induced injury. Methods. PMECs were divided into 6 groups: normal control, TNF-α (10 ng/mL TNF-α), Dex (1×10-6 M Dex + 10 ng/mL TNF-α), CRT high (1000 ng/mL CRT + 10 ng/mL TNF-α), CRT medium (500 ng/mL CRT + 10 ng/mL TNF-α), and CRT low group (250 ng/mL CRT + 10 ng/mL TNF-α). Cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Cell micromorphology was observed under transmission electron microscope. The localization and expression of tight junction proteins Claudin-5 and ZO-1 were analyzed by immunofluorescence staining and Western blot, respectively. Results. TNF-a had successfully induced an acute endothelial cell injury model. Dex and CRT treatments had significantly stimulated the growth and reduced the apoptosis of PMECs (all p < 0.05 or 0.01) and alleviated the TNF-α-induced cell injury. The expression of Claudin-5 and ZO-1 in Dex and all 3 CRT groups was markedly increased compared with TNF-a group (all p < 0.05 or 0.01). Conclusion. CRT effectively protects PMECs from TNF-α-induced injury, which might be mediated via stabilizing the structure of tight junction. CRT might be a promising, effective, and safe therapeutic agent for the treatment of ALI.

scholarly journals Effects of Lipotoxicity in Brain Microvascular Endothelial Cells During Sirt3 Deficiency-Potential Role in Comorbid Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Alpna Tyagi ◽  
Carol Mirita ◽  
Iman Shah ◽  
P. Hemachandra Reddy ◽  
Subbiah Pugazhenthi
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Palmitic Acid ◽  
Inflammatory Mediators ◽  
Vascular Endothelial Cells ◽  
Microvascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Tight Junction Proteins ◽  
The Brain ◽  
Junction Proteins

Silence information regulator 3 (SIRT3) is an NAD+ dependent deacetylase enzyme that enhances the function of key mitochondrial proteins. We have earlier demonstrated that deletion of Sirt3 gene leads to downregulation of metabolic enzymes, mitochondrial dysfunction and neuroinflammation in the brain, the major causes of Alzheimer’s disease (AD). We also reported recently that Sirt3 gene deletion in Alzheimer’s transgenic mice leads to exacerbation of neuroinflammation, amyloid plaque deposition and microglial activation. AD often coexists with other brain lesions caused by comorbidities which can exert their deleterious effects through the neurovascular unit. This unit consists of brain microvascular endothelial cells (BMECs), end feet of astrocytes, and pericytes. BMECs are uniquely different from other vascular endothelial cells because they are glued together by tight-junction proteins. BMECs are in constant contact with circulating factors as they line the luminal side. Therefore, we hypothesized that vascular endothelial injury caused by comorbidities plays a significant role in neuroinflammation. Herein, we investigated the effects of lipotoxicity in BMECs and how Sirt3 deficiency facilitate the deleterious effects of lipotoxicity on them using in vivo and in vitro models. We observed decreases in the levels of SIRT3 and tight junction proteins in the brain samples of western diet-fed APP/PS1 mice. Similar observations were obtained with Alzheimer’s post-mortem samples. Exposure of BEND3 cells, mouse brain-derived Endothelial cells3, to a combination of high glucose and palmitic acid resulted in significant (P &lt; 0.01-P &lt; 0.001) decreases in the levels of SIRT3, claudin-5 and ZO-1. Induction of inflammatory mediators, including Cox-2, CXCL1, RANTES, and GADD45β was also observed in these treated cells. Interestingly, the induction was more with Sirt3-silenced BEND3 cells, suggesting that Sirt3 deficiency exacerbates inflammatory response. Palmitic acid was more potent in inducing the inflammatory mediators. Significant cytotoxicity and changes in microglial morphology were observed when cocultures of Sirt3-silenced BEND3 and Sirt3-silenced BV2 cells were exposed to palmitic acid. Transendothelial electrical resistance measurement with these cocultures suggested decreased barrier integrity. The findings of this study suggest that hyperlipidemia in comorbidities can compromise blood brain barrier integrity by inducing inflammatory mediators and decreasing tight junction proteins in the vascular endothelial cells of the AD brain, leading to activation of microglia.

scholarly journals Interleukin-34 Restores Blood–Brain Barrier Integrity by Upregulating Tight Junction Proteins in Endothelial Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115981 ◽  
Author(s):  
Shijie Jin ◽  
Yoshifumi Sonobe ◽  
Jun Kawanokuchi ◽  
Hiroshi Horiuchi ◽  
Yi Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity ◽  
Junction Proteins
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