scholarly journals Blockade of Angiotensin II Attenuates VEGF-Mediated Blood—Retinal Barrier Breakdown in Diabetic Retinopathy

2008 ◽  
Vol 29 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Jeong Hun Kim ◽  
Jin Hyoung Kim ◽  
Young Suk Yu ◽  
Chang Sik Cho ◽  
Kyu-Won Kim
Keyword(s):  
Diabetic Retinopathy ◽  
Angiotensin Ii ◽  
Tight Junction ◽  
Vascular Permeability ◽  
Ace Inhibitor ◽  
Ang Ii ◽  
Tight Junction Proteins ◽  
Blood Retinal Barrier ◽  
Brb Breakdown ◽  
Junction Proteins

Diabetic retinopathy (DR) is the leading cause of vision loss as a major complication of diabetes mellitus. The blood—retinal barrier (BRB) breakdown is a critical early event in the pathogenesis of DR. It has been known that the rennin-angiotensin system (RAS) is important in the progression of the DR via angiotensin II (Ang II), the effector of RAS. In this study, we showed that blockade of Ang II attenuates vascular endothelial growth factor (VEGF)-mediated BRB breakdown in DR. In streptozotocin-induced diabetes, retinal vascular permeability increased with upregulation of VEGF, where Ang II and its receptors were upregulated. Ang II induced VEGF expression in retinal endothelial cells accompanied by loss of tight junction proteins. However, the blockade of Ang II by perindopril, an angiotensin converting enzyme (ACE) inhibitor, inhibited upregulation of VEGF, and prevented the loss of tight junction proteins. Moreover, inhibition of Ang II by perindopril attenuated increased vascular permeability of diabetic retina accompanied by recovery of tight junction proteins in retinal vessels. Therefore, we suggest that the RAS involves in increased vascular permeability during early stage of DR, which is mediated by VEGF. Furthermore, the ACE inhibitor may have a therapeutic potential in the treatment of diabetic BRB breakdown.

scholarly journals Decursin Inhibits VEGF-Mediated Inner Blood—Retinal Barrier Breakdown by Suppression of VEGFR-2 Activation

2009 ◽  
Vol 29 (9) ◽  
pp. 1559-1567 ◽  
Author(s):  
Jin Hyoung Kim ◽  
Jeong Hun Kim ◽  
You Mie Lee ◽  
Eun-Mi Ahn ◽  
Kyu-Won Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Vision Loss ◽  
Retinal Vessels ◽  
Tight Junction Proteins ◽  
Blood Retinal Barrier ◽  
Retinal Endothelial Cells ◽  
Extracellular Signal ◽  
Brb Breakdown ◽  
Junction Proteins

The blood—retinal barrier (BRB) is essential for the normal structural and functional integrity of the retina, whose breakdown could cause the serious vision loss. Vascular endothelial growth factor (VEGF), as a permeable factor, induces alteration of tight junction proteins to result in BRB breakdown. Herein, we demonstrated that decursin inhibits VEGF-mediated inner BRB breakdown through suppression of VEGFR-2 signaling pathway. In retinal endothelial cells, decursin inhibited VEGF-mediated hyperpermeability. Decursin prevented VEGF-mediated loss of tight junction proteins including zonula occludens-1 (ZO-1), ZO-2, and occludin in retinal endothelial cells, which was also supported by restoration of tight junction proteins in intercellular junction. In addition, decursin significantly inhibited VEGF-mediated vascular leakage from retinal vessels, which was accompanied by prevention of loss of tight junction proteins in retinal vessels. Decursin significantly suppressed VEGF-induced VEGFR-2 phosphrylation that consequently led to inhibition of extracellular signal-regulated kinase (ERK) 1/2 activation. Moreover, decursin induced no cytotoxicity to retinal endothelial cells and no retinal toxicity under therapeutic concentrations. Therefore, our results suggest that decursin prevents VEGF-mediated BRB breakdown through blocking of loss of tight junction proteins, which might be regulated by suppression of VEGFR-2 activation. As a novel inhibitor to BRB breakdown, decursin could be applied to variable retinopathies with BRB breakdown.

scholarly journals Eucalyptol Blocks Diabetes-Associated Disruption of Tight Junction and Blood Retinal Barrier in Retinal Pigment Epithelial Cells and Diabetic Eyes

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 413-413
Author(s):  
Dongyeon Kim ◽  
Min-kyung Kang ◽  
Young-Hee Kang
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Tight Junction Proteins ◽  
Blood Retinal Barrier ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells ◽  
Junction Proteins

Abstract Objectives Diabetes-associated retinal impairment has been implicated in diabetic retinopathy. Chronic hyperglycemia leads to disruption of tight junction and breakdown of blood retinal barrier. Eucalyptol is a natural organic essential oil and a monoterpenoid present in eucalyptus oil with anti-inflammatory, anti-diabetic and antioxidant properties. Methods Primary human retinal pigment epithelial cells (HRPEC) were cultured in media containing 33 mM glucose for 4 days in the presence of 1–20 μM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Cell lysates and mouse eye tissue extracts were prepared for Western blotting, in which antibodies of ZO-1, occludin, matrix metalloproteinase (MMP)-2 and MMP-9 were used. Results Eucalyptol enhanced epithelial induction of the tight junction proteins of ZO-1 and occludin reduced by glucose loading. Consistently, oral administration of eucalyptol to db/db mice augmented the eye tissue levels of these tight junction proteins. In addition, the induction of MMP-2 and MMP-9 involved in the degradation of extracellular matrix, was elevated by exposure of glucose to HRPEC, which was encumbered by eucalyptol in a dose-dependent manner. Conclusions These results demonstrated that eucalyptol maintained transepithelial cells integrity and blood retinal barrier in diabetic eyes. Therefore, eucalyptol may be a potent retinoprotective agent combating diabetes-associated retinal malfunction. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2017R1A6A3A04011473).

scholarly journals Dendrobium chrysotoxumLindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Zengyang Yu ◽  
Chenyuan Gong ◽  
Bin Lu ◽  
Li Yang ◽  
Yuchen Sheng ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Tight Junction ◽  
Diabetic Rats ◽  
Intercellular Adhesion Molecule ◽  
Tight Junction Proteins ◽  
Intercellular Adhesion Molecule 1 ◽  
Traditional Chinese Herbal Medicine ◽  
Junction Protein ◽  
Retinal Inflammation ◽  
Junction Proteins

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract ofDendrobium chrysotoxumLindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factorα(TNFα), interleukin- (IL-) 6, and IL-1βin diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ(IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1.

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

2016 ◽  
Vol 232 (5) ◽  
pp. 1123-1134 ◽  
Author(s):  
Jang-Hyuk Yun ◽  
Sung Wook Park ◽  
Kyung-Jin Kim ◽  
Jong-Sup Bae ◽  
Eun Hui Lee ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Tight Junction ◽  
Vascular Leakage ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals Luo Tong Formula Alleviates Diabetic Retinopathy in Rats Through Micro-200b Target

2020 ◽  
Vol 11 ◽  
Author(s):  
Bing Pang ◽  
Qing Ni ◽  
Sha Di ◽  
Li-juan Du ◽  
Ya-li Qin ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Glucose ◽  
Tight Junction ◽  
Diabetic Rats ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Blood Retinal Barrier ◽  
Tissue Samples ◽  
Brb Breakdown

Aim: Diabetic retinopathy (DR) is a serious complication of diabetes (DM). Luo Tong formula (LTF) exerts protective effects against DR in rats, but its underlying mechanism remains unknown. Methods: Sprague-Dawley rats injected with streptozotocin (STZ) were used as an experimental diabetes model. LTF or calcium dobesilate (CaD) was administered to diabetic rats via gastric gavage. After the 12 weeks of treatment, blood and tissue samples were collected to determine serum glucose and retinal structure. Blood samples were collected for blood glucose and hemorheology analysis. Gene or protein expression levels were evaluated by immunohistochemistry, western blotting and/or quantitative real-time polymerase chain reaction (PCR). Results: DM rats exhibits significantly increased blood retinal-barrier (BRB) breakdown and VEGF/VEGFR expression in the retina, and decreased miR-200b and tight junction ZO-1/Occludin/ Claudin-5 genes expression, as well as Ang-1/Tie-2 expressions in the retina compared to normal control group. LTF treatment significantly moderated histological abnormalities in diabetic rats, independent of blood glucose level; improved some hemorrheological parameters; decreased the expressions of VEGF/VEGFR and BRB breakdown, significantly increased PEDF and tight junction proteins ZO-1/Occludin, as well as increased retinal miR-200b expression compared to non-treatment diabetic rats. Moreover, LTF prevented the reduction in Ang-1/Tie-2 expression. Conclusions: LTF treatment ameliorated DR through its repair vascular and attenuate vascular leakage. A mechanism involving miR-200b may contribute to benefit effects.

scholarly journals Relationship of Cx43 regulation of vascular permeability to osteopontin-tight junction protein pathway after sepsis in rats

2018 ◽  
Vol 314 (1) ◽  
pp. R1-R11 ◽  
Author(s):  
Jie Zhang ◽  
Guangming Yang ◽  
Yu Zhu ◽  
Xiaoyong Peng ◽  
Tao Li ◽  
...  
Keyword(s):  
Tight Junction ◽  
Vascular Permeability ◽  
Pulmonary Vein ◽  
Vascular Endothelial Cells ◽  
Pulmonary Veins ◽  
Cecal Ligation ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
And Migration ◽  
Junction Proteins

Our previous study demonstrated that connexin (Cx)43 participated in the regulation of vascular permeability in severe sepsis. Osteopontin (OPN) has been demonstrated to participate in the occurrence of atherosclerosis, inflammation, as well as the adhesion and migration of cells. It is not clear whether OPN is involved in Cx43 regulating vascular permeability after sepsis and if it is related to tight-junction proteins. with the use of cecal ligation and puncture (CLP)-induced septic rats and lipopolysaccharide (LPS)-treated pulmonary vein vascular endothelial cells (VECs), the role of zona occuldens 1 (ZO-1) and claudin-5 in Cx43 regulation of vascular permeability and its relationship to OPN were investigated in the present study. The results showed that the expression of ZO-1 and claudin-5 in pulmonary vein were decreased in CLP rats and LPS-treated pulmonary vein VECs. Cx43-overexpressed lentivirus induced the degradation of ZO-1 and claudin-5, while Cx43 RNAi lentivirus abrogated the degradation of ZO-1 and claudin-5 induced by LPS. The vascular permeability and expression of OPN in pulmonary veins were significantly increased in CLP rats and LPS-treated pulmonary vein VECs. Silencing OPN by OPN RNAi lentivirus inhibited the vascular hyperpermeability induced by LPS. Overexpressed Cx43 lentivirus increased the expression of OPN and vascular permeability and downregulated the expression of ZO-1 and claudin-5 in pulmonary vein VECs. Silencing OPN by OPN RNAi lentivirus inhibited the effects of Cx43-overexpressed lentivirus on downregulation of ZO-1 and claudin-5 and vascular hyperpermeability in pulmonary vein VECs. Transfection of specific double-stranded RNA targeting to β-catenin and T-cell factor-4 (Tcf-4) abolished the upregulation of OPN induced by Cx43 overexpression. These results suggest that OPN participates in the regulation of vascular permeability by Cx43 after sepsis. Cx43 upregulation of OPN is via the Tcf-4/β-catenin transcription pathway; OPN increases vascular permeability by downregulating the expression of the tight junction proteins ZO-1 and claudin-5.

Tight junction proteins in HCC and metastatic liver tumours

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
Cs Páska ◽  
E Orbán ◽  
A Kiss ◽  
Zs Schaff ◽  
A Szijjártó ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junction Proteins ◽  
Liver Tumours ◽  
Metastatic Liver ◽  
Junction Proteins
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