Recently, we found that ZO-1, a tight junction-associated protein, was concentrated in the so called isolated adherens junction fraction from liver (Itoh, M., A. Nagafuchi, S. Yonemura, T. Kitani-Yasuda, Sa. Tsukita, and Sh. Tsukita. 1993. J. Cell Biol. 121:491-502). Using this derived chick as an antigen, obtained three monoclonal antibodies specific for approximately 65-kD protein rats. This antigen not extractable plasma membranes without detergent, suggesting it is integral membrane...

Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids. Immunofluorescence laser scan microscopy revealed that chick full-length occludin introduced into human bovine epithelial cells was correctly delivered to incorporated preexisting TJ. Further transfection studies various deletion mutants showed the E, especially its approximately 150 acids E358/504),...

ABSTRACT Endothelial cells provide a crucial interface between blood and tissue environments. Free diffusion of substances across endothelia is prevented by the endothelial tight junction, permeability which varies enormously depending on tissue. blood-brain barrier possess junctions severely limited permeability, whereas those non-neural are considerably leakier, but molecular basis for this difference not clear. Occludin major transmembrane protein localizing at junction. In study, we...

Occludin has been identified from chick liver as a novel integral membrane protein localizing at tight junctions (Furuse, M., T. Hirase, M. Itoh, A. Nagafuchi, S. Yonemura, Sa. Tsukita, and Sh. Tsukita. 1993. J. Cell Biol. 123:1777-1788). To analyze modulate the functions of junctions, it would be advantageous to know mammalian homologues occludin their genes. Here we describe nucleotide sequences full length cDNAs encoding rat-kangaroo (potoroo), human, mouse, dog. Rat-kangaroo cDNA was...

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. Therefore, augmentation of eNOS expression or production by pharmacological intervention postulated to inhibit We crossed eNOS-overexpressing (eNOS-Tg) mice with atherogenic apoE-deficient (apoE-KO) determine whether overexpression in the endothelium could development After 8 weeks on high-cholesterol diet, atherosclerotic lesion areas aortic sinus were unexpectedly...

In epithelial and endothelial cells, tight junctions regulate the paracellular permeability of ions proteins. Disruption by inflammation is often associated with tissue edema, but regulatory mechanisms are not fully understood. Using ECV304 cells as a model system, lysophosphatidic acid histamine were found to increase tracer horseradish peroxidase. Cytoskeletal changes induced these agents included stimulation stress fiber formation myosin light chain phosphorylation. Additionally,...

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. Therefore, augmentation of eNOS expression or production by pharmacological intervention postulated to inhibit We crossed eNOS-overexpressing (eNOS-Tg) mice with atherogenic apoE-deficient (apoE-KO) determine whether overexpression in the endothelium could development After 8 weeks on high-cholesterol diet, atherosclerotic lesion areas aortic sinus were unexpectedly...

ABSTRACT Occludin is an integral membrane protein localizing at tight junctions with four transmembrane domains. When chicken occludin was overexpressed in insect cells by recombinant baculovirus infection, peculiar multilamellar structures accumulated the cytoplasm. Partial isolation of these indicated that introduced highly enriched structures. Thin section electron microscopy revealed each lamella transformed from intracellular membranous cisternae whose luminal space completely...

Monocyte/macrophage infiltration to the arterial wall is an initial step in atherosclerosis, and monocyte chemoattractant protein-1 (MCP-1) thought play a central role recruitment of these cells. In present study, we examined local expression MCP-1 at vessel initiation development atherosclerosis. We transfected cDNA encoding rat into rabbit carotid artery with use hemagglutinating virus Japan (HVJ)-liposome method. The rabbits were divided following groups: (1) those fed normal chow...

Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ameliorates hyperglycemia in patients with type diabetes (T2D) by inducing sustained glucosuria. Empagliflozin treatment was previously associated transient increase 24-h urine volume Caucasian T2D, however comparable evidence Japanese T2D individuals is scarce. We therefore assessed acute and chronic changes fluid intake empagliflozin T2D.In this randomized, double-blind, placebo-controlled, parallel-group, multiple-dose,...

Background and Purpose— Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle artery, statins were shown to reduce infarct size. However, effect on hypertension-based stroke is unknown. The purpose this study clarify statin in stroke-prone spontaneously hypertensive rats (SHR-SP), which both hemorrhage...

Chronic inflammation in arterial wall that is driven by immune cells and cytokines plays pivotal roles the development of atherosclerosis. Interleukin 27 (IL-27) a member IL-12 family consists IL-27p28 Epstein-Barr virus induced gene 3 (EBI3) has anti-inflammatory properties regulate T cell polarization cytokine production. IL-27-deficient ( Ldlr−/− Ebi3−/−) IL-27 receptor-deficient WSX-1−/−) mice were generated fed with high-cholesterol diet to induce Roles bone marrow-derived vivo...

Pentraxin-3 (PTX3) reportedly has protective roles in atherosclerosis and myocardial infarction, is a useful biomarker of vascular inflammation. However, the detailed functions PTX3 inflammation are yet to be elucidated. This study aimed investigate function macrophages.PMA-treated THP-1 cell line (THP-1 macrophage) monocyte-derived human primary macrophages were treated with recombinant PTX3. Cytokine chemokine levels culture medium measured as well monocyte chemoattractant protein (MCP-1)...

Obesity prevalence has increased in Japan recent years. Given the strong association of obesity with poor glycemic control, and risk type 2 diabetes (T2D) central obesity, this study describes current trends relationships between glycated hemoglobin (HbA1c), body mass index (BMI), waist circumference Japanese people T2D. This was a retrospective, cross-sectional T2D who had at least one recorded HbA1c BMI (or circumference) value Medical Data Center Claims database. Five annual cohorts...

Endogenous nitric oxide (NO) inhibits the contractile response to beta-adrenergic stimulation, but its effect on cardiac hypertrophy mediated by beta-adrenoceptors remains unclear. The present study was designed determine whether overproduction of endothelial NO synthase (eNOS) could inhibit induced chronic isoproterenol (ISO) infusion (30mg/kg per day) using eNOS overexpressing (eNOS-Tg) mice and wild-type (WT) mice. In a separate group, WT were treated with ISO hydralazine decrease blood...

Abstract Aim To assess the safety and efficacy of tirzepatide in people East Asian descent based on age body mass index (BMI). Materials Methods Data participants enrolled countries SURPASS‐1, ‐3, ‐4, ‐5, J‐mono J‐combo phase 3 clinical trials were included. Participants with type 2 diabetes a baseline HbA1c 7.0% up to 11.0% BMI 23 kg/m or greater 25 treated 5, 10 15 mg evaluated (94% from Japan) (< 65 ≥ years) ). Key outcomes assessed. Results At baseline, 73% had 74% younger than years....

The objective of this work was to assess the association tirzepatide with changes in insulin sensitivity and beta-cell function Japanese patients type 2 diabetes (T2D). This a prespecified analysis SURPASS J-mono, multicenter, randomized, double-blind, active-controlled phase 3 study participants T2D. Participants were randomly assigned receive 5, 10, 15 mg, or dulaglutide 0.75 mg once weekly for 52 weeks. Changes from baseline homeostatic model assessment (HOMA2) parameters assessed by...

BackgroundSeveral studies have reported the cost-effectiveness of sodium-glucose co-transporter 2 inhibitors in heart failure patients; however, their economic implications not been sufficiently elucidated Japan.MethodsA Markov cohort model was developed to evaluate empagliflozin plus standard care (SoC) vs. SoC for patients with reduced ejection fraction (HFrEF) Japan. Model inputs, including risk clinical events, costs, and utilities based on Kansas City Cardiomyopathy Questionnaire...

Objective: Vascular endothelial growth factor (VEGF) is a potent angiogenic and plays an important pathophysiological role in the maintenance of tissue structure as well regeneration after ischemic injury. Three-hydroxy-3methylglutaryl-CoA reductase inhibitors reduce vascular inflammation induce angiogenesis. This study examined whether simvastatin stimulates VEGF expression cells nature its underlying mechanism. Methods Results: Simvastatin induced mRNA protein secretion that were reversed...