Identification of the inhibitory factor for the transcription of inflammatory genes in vascular smooth muscle cells

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2004～2005課題番号: 16590877研究代表者: 西尾 善彦（滋賀医科大学・医学部・講師

Elucidation of the mechanism for the activation of transcription factors and gene response in the aorta of the Postprandial state of rata

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2006～2007課題番号: 18590981研究代表者: 西尾 善彦（滋賀医科大学・医学部・講師

Identification of oxidative stress related genes and transcription factors in vascular tissues

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 1999～2001課題番号: 11671112研究代表者: 西尾 善彦（滋賀医科大学・医学部・助手

A novel effect of insulin on vascular smooth muscle cells through the transcriptional regulation ?the meaning of the activation of C/EBP

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2002～2003課題番号: 14571090研究代表者: 西尾 善彦（滋賀医科大学・医学部・助手

Multimodality imaging of biatrial myxomas in an asymptomatic patient

AbstractMyxomas are located in the left atrium in 75–80% of cases and almost always present with signs and symptoms of a thromboembolic event. Biatrial myxomas are rare, and their incidence is generally less than 2.5% of all myxomas. We herein present a case of biatrial myxomas as an incidental finding by echocardiography where the patient underwent surgery. Echocardiography continues to be the initial imaging modality for intracardiac masses. Cardiac magnetic resonance provides superior tissue characterization, particularly important in differentiating a myxoma from a thrombus. Appropriate use of these non-invasive imaging modalities may lead to a correct diagnosis and good outcome.<Learning objective: In this report we present a rare case of cardiac biatrial myxomas. Multimodality imaging, especially delayed enhancement cardiac magnetic resonance imaging, provided specific findings for the diagnosis.

Elucidation of the mechanism for the activation of transcription factors and gene response in the aorta of the postprandial state ofrata

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2005～2007課題番号: 17390262研究代表者: 柏木 厚典（滋賀医科大学・医学部・教授）研究分担者: 前川 聡（滋賀医科大学・医学部・准教授）研究分担者: 西尾 善彦（滋賀医科大学・医学部・講師

Cross-link of signal transduction and channel function diabetic neuropathy

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 1997～1999課題番号: 09670652研究代表者: 安田 斎（滋賀医科大学・医学部・講師）研究分担者: 北里 宏（滋賀医科大学・医学部・名誉教授）研究分担者: 寺田 雅彦（滋賀医科大学・医学部・助教授）研究分担者: 西尾 善彦（滋賀医科大学・医学部・助手

Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis : the PROTECT study

Background: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus. Methods: A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50–100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies. Discussion: The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis

GW501516, a PPARδ Agonist, Ameliorates Tubulointerstitial Inflammation in Proteinuric Kidney Disease via Inhibition of TAK1-NFκB Pathway in Mice

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(−). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection