Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression

2015 ◽  
Vol 65 (3) ◽  
pp. 213-224 ◽  
Author(s):  
Jie Chen ◽  
Jun Wang ◽  
Chenglei Su ◽  
Wenyi Qian ◽  
Li Sun ◽  
...  
Keyword(s):  
Trypsin Inhibitor ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Urinary Trypsin Inhibitor ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Vascular Endothelial Cadherin

scholarly journals S-1-Propenylcysteine Improves TNF-α-Induced Vascular Endothelial Barrier Dysfunction by Suppressing the GEF-H1/RhoA/Rac Pathway

2020 ◽  
Author(s):  
Kayo Kunimura ◽  
Satomi Miki ◽  
Miyuki Takashima ◽  
Jun-ichiro Suzuki
Keyword(s):  
Barrier Function ◽  
Vascular Diseases ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Junctional Proteins ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Sulfur Containing

Abstract Background: Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively. Results: We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to protect the disruption of junctional proteins on the cell-cell contact regions and the increase of actin stress fibers induced by TNF-α. Conclusions: The present study suggested that AGE and S1PC improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane.

scholarly journals Vascular Endothelial Barrier Dysfunction Mediated by Amyloid-β Proteins

2009 ◽  
Vol 17 (4) ◽  
pp. 845-854 ◽  
Author(s):  
Enika Nagababu ◽  
Peter V. Usatyuk ◽  
Divya Enika ◽  
Viswanathan Natarajan ◽  
Joseph M. Rifkind
Keyword(s):  
Amyloid Β ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction

scholarly journals S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kayo Kunimura ◽  
Satomi Miki ◽  
Miyuki Takashima ◽  
Jun-ichiro Suzuki
Keyword(s):  
Barrier Function ◽  
Vascular Diseases ◽  
Endothelial Barrier ◽  
Major Constituent ◽  
Vascular Endothelial ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Junctional Proteins ◽  
Tnf Α ◽  
Sulfur Containing

Abstract Background Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway. Methods Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively. Results We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to prevent the disruption of junctional proteins on the cell–cell contact regions and the increase of actin stress fibers induced by TNF-α. Conclusions The present study suggested that AGE and its major constituent, S1PC, improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane.

scholarly journals S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway

2020 ◽  
Author(s):  
Kayo Kunimura ◽  
Satomi Miki ◽  
Miyuki Takashima ◽  
Jun-ichiro Suzuki
Keyword(s):  
Barrier Function ◽  
Vascular Diseases ◽  
Endothelial Barrier ◽  
Major Constituent ◽  
Vascular Endothelial ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Junctional Proteins ◽  
Tnf Α ◽  
Sulfur Containing

Abstract Background: Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively.Results: We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to prevent the disruption of junctional proteins on the cell-cell contact regions and the increase of actin stress fibers induced by TNF-α.Conclusions: The present study suggested that AGE and its major constituent, S1PC, improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane.

scholarly journals Chlorogenic acid alleviates sepsis-induced endothelial barrier dysfunction and the underlying mechanism

2020 ◽  
Author(s):  
Zisen Zhang ◽  
Yue Wu ◽  
Yu Zhu ◽  
Xiao-yong Peng ◽  
Ming-ying Xue ◽  
...  
Keyword(s):  
Septic Shock ◽  
Underlying Mechanism ◽  
Shock Group ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Endothelial Barrier Function ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Liver And Kidney ◽  
Kidney Blood Flow

Abstract Background Chlorogenic acid (CGA) has been shown to improve inflammatory cytokines in patients with ulcerative colitis. Vascular endothelial barrier dysfunction is closely related to sepsis. We hypothesize that CGA plays an important role in treating sepsis by protecting the mesenteric endothelial barrier. Methods Severe sepsis was established by cecal ligation and puncture (CLP) in SD rats. Immediately after the induction of sepsis, CGA (20 mg/kg) was administered intravenously, and the effects of CGA on mesenteric vascular leakage, hemodynamics, liver and kidney blood flow, and the ultrastructure of the mesenteric endothelial cells were determined. The transendothelial electrical resistance and the Transwell permeability assays were used for observing endothelial barrier function in vascular endothelial cells (VECs). ZO-1 and VE-cadherin expression were observed by immunohistochemistry and western blotting. Results FITC-BSA leakage from mesenteric micro-vessels was significantly increased after septic shock, which was significantly improved by CGA. Liver and kidney blood flow were increased by 41.2% and 38.4%, respectively, after CGA administration compared with the septic shock group. Hemodynamic status was significantly decreased after septic shock, and significantly improved by CGA. The 72-h survival rate of septic shock rats in the CGA group (50%) was significantly higher than the septic shock group (6.25%). CGA improved the tight junction opening after septic shock and also significantly up-regulated the expression of ZO-1 and VE-cadherin. CGA also protected endothelial hyperpermeability against lipopolysaccharide-stimulated VEC injury by increasing the expression of ZO-1 and VE-cadherin in vitro. Conclusion CGA was beneficial for endothelial barrier function in rats with septic shock, which is the major contribution to CGA with respecting to improving hemodynamic status and organ perfusion. The underlying mechanism involved CGA up-regulation of ZO-1 and VE-cadherin.

scholarly journals ASK1-p38 cascaded signal mediates pulmonary microvascular endothelial barrier injury induced by the return of PHSML in rats

RSC Advances ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 4870-4875
Author(s):  
Muhammad Fawad ◽  
Muhammad Abbas ◽  
Limin Zhang ◽  
Yuping Zhang ◽  
Yaxiong Guo
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Mesenteric Lymph ◽  
Microvascular Endothelial

The return of post-hemorrhagic shock mesenteric lymph (PHSML) induces pulmonary vascular endothelial barrier dysfunction, which results in acute lung injury.

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